Glycopeptide Antibiotic Monomer Derivatives

ABSTRACT

Novel glycopeptide antibiotic derivatives. These derivatives are represented by the formula (aglycon part of glycopeptide antibiotic derivative)-(Sac-NH)—R A  [wherein (aglycon part of glycopeptide antibiotic derivative) is the part formed by removing the sugar part from a known glycopeptide antibiotic derivative; (Sac-NH) part is an amino sugar part or a sugar chain part containing an amino sugar; and R A  represents, e.g., the formula —X 1 —Ar 1 —X 2 —Y—X 3 —Ar 2  (wherein X 1 , X 2 , and X 3  each represents 1) a single bond or 2) a heteroatom or heteroatom-containing group selected from the group consisting of —N═, ═N—, —NR 1 —, —O—, etc.; Y represents —NR 2 CO— or —CONR 2 — (wherein R 2  represents hydrogen or lower alkyl), etc.)]. These derivatives have antibacterial activity against vancomycin-resistant bacteria.

TECHNICAL FIELD

The invention relates to a glycopeptide antibiotic derivative and a pharmaceutical formulation comprising such derivative.

BACKGROUND OF THE INVENTION

Glycopeptide antibiotics, which have a complex polycyclic peptide structure, are produced in various microorganism and effective to most gram-positive bacteria as an antimicrobial. In recent years, there are emergences of drug-resistant strains such as penicillin-resistant, cephalosporin-resistant, and serious problems of infections with multidrug resistant and methicillin-resistant Staphylococcus aureus (MRSA) has been raised in clinical practice. Glycopeptide antibiotics, such as vancomycin, are effective typically to these resistant strains, and vancomycin has been a drug as an ultimate tool for infections with MRSA and other resistant strains.

In certain strains, however, there is growing concern of emergence of resistance to vancomycin, such as vancomycin-resistant enterococci (VRE). VRE has a different mechanism and degree of resistance, depending on the gene type of a resistance-related gene such as Van A, B, C, D, E, G. For example, teicoplanin, which is a glycopeptide antibiotic as with vancomycin, is effective to Van B type VRE. On the other hand, effective glycopeptide antibiotic has not been released for Van A type VRE, while clinical measures to fight such resistant strain is especially needed. Furthermore, Staphylococcus aureus that has acquired the resistance of VRE (VRSA) has been discovered recently. Therefore, need for development of glycopeptide derivative having improved activity and/or selectivity exists. Many vancomycins and other glycopeptide derivatives have been known in the art. See, e.g., references as follows.

(1) Japanese Patent Publication 61-251699

(2) Japanese Patent Publication 7-258289

(3) WO96/30401

(4) WO00/39156

(5) Japanese Patent Publication 2000-302687

(6) WO2004/44222

(7) WO2001/81372

SUMMARY OF THE INVENTION

The invention relates to a novel glycopeptide antibiotic derivative that has an increased and improved property compared with that of conventional glycopeptide antibiotics. Certain glycopeptide derivatives of the invention, particularly vancomycin derivatives, show an increased antimicrobial activity compared with vancomycin itself.

The invention provides:

(1) A compound of the formula:

(aglycon part of glycopeptide antibiotic derivative)-(Sac-NH)—R^(A) or a pharmaceutically acceptable salt or solvate thereof, wherein,

-   -   “(aglycon part of glycopeptide antibiotic derivative)” is a part         of known glycopeptide antibiotic derivative from which a sugar         moiety has been removed:     -   “(Sac-NH)” is an amino sugar or an amino sugar-containing sugar         chain;     -   R^(A) is presented by the formula:         —X¹—Ar¹—X²—Y—X³—Ar²     -   wherein X¹, X² and X³ are independently         -   1) single bond;         -   2) a heteroatom-containing group selected from the group             consisting of —N═, ═N—, —NR¹— wherein R¹ is hydrogen or             lower alkyl, —O—, —S—, —SO— and —SO₂—, or a linkage thereof;             or         -   3) optionally substituted alkylene or alkenylene optionally             interrupted by one or more same or different heteroatomic             group;     -   Y is —NR²CO—, —CONR²— wherein R² is hydrogen or lower alkyl, or         a group of the formula:         wherein R³ is alkylene; and

Ar¹ and Ar² are independently a carbocycle or heterocycle which is optionally substituted and may have an unsaturated bond.

Preferably, the formula:

more preferably, the formula:

wherein,

-   -   R^(A) is as defined above;     -   R^(B) is —OH, —NR⁵R⁵′ wherein R⁵ and R⁵′ are independently         hydrogen, optionally substituted alkyl, —NH—R, —NH—COR,         —NH—CONHR, —O—R wherein each R is independently hydrogen or         optionally substituted alkyl or amino sugar residue, or —OR⁶         wherein R⁶ is optionally substituted alkyl that may comprise a         heteroatomic group;

R^(C) is hydrogen or optionally substituted alkyl that may comprise a heteroatomic group, preferably —NH—; and

R^(D) is hydrogen or lower alkyl,

R is optionally substituted alkyl, with the proviso that (aglycon part of glycopeptide antibiotic derivative)-(Sac-NH) moiety is not represented by the formula:

wherein R is sugar residue.

(2) A pharmaceutical formulation, preferably an antimicrobial formulation, comprising the compound, pharmaceutically acceptable salt or solvate thereof of the present invention as described above.

The invention is also relates to a compound, a pharmaceutically acceptable salt or solvate thereof as described above in (1) and a pharmaceutical composition as described above in (2), excluding that R^(A) is 4-(monofluorobenzoylamino)benzyl.

The invention is also relates to a compound, a pharmaceutically acceptable salt or solvate thereof as described above in (1) and a pharmaceutical composition as described above in (2), excluding that Ar¹ is phenylene, Y is —NR²CO—, and Ar² is monofluorophenyl.

The invention is also relates to a compound, a pharmaceutically acceptable salt or solvate thereof as described above in (1) and a pharmaceutical composition as described above in (2), excluding that Ar² is monofluorophenyl.

The invention is also relates to a compound, a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical formulation, preferably antimicrobial formulation comprising the same, as described in the following (3) to (18).

(3) The compound according to (1) wherein Y is —NR²CO— or —CONR²— wherein R² is hydrogen or lower alkyl;

(4) The compound according to (1) wherein Ar¹ and Ar² are optionally substituted aryl, or optionally substituted heteroaryl, optionally substituted heterocycle, or optionally substituted cycloalkyl;

(5) The compound according to (1) wherein Ar¹ and Ar² are optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle, or optionally substituted cycloalkyl, and Y is —NHCO— or —CONH—;

(6) The compound according to (1) wherein X¹ is lower alkylene;

(7) The compound according to (1) wherein X² is a single bond, lower alkylene or a heteroatomic group as described above;

(8) The compound according to (1) wherein X³ is a single bond, lower alkylene or a heteroatomic group as described above

(9) The compound according to (1) wherein X¹ is lower alkylene; X² is a single bond, lower alkylene or a heteroatomic group as described above; X³ is a single bond, lower alkylene or a heteroatomic group as described above; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocycle, or optionally substituted cycloalkyl; and Ar² is optionally substituted phenyl, optionally substituted heterocycle or optionally substituted cycloalkyl.

(10) The compound according to (1) wherein X¹ is lower alkylene; X² and X³ are independently a single bond, lower alkylene or a heteroatomic group as described above; Y is a group of the formula:

wherein R³ is alkylene;

Ar¹ is optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocycle, or optionally substituted cycloalkyl; and Ar² is optionally substituted aryl, optionally substituted heterocycle or optionally substituted cycloalkyl;

(11) The compound of any one of (1) to (10) wherein Ar² is any one of aryl, heterocycle or fused rings of the formula:

that is optionally substituted with one or more of the substituent selected from the group consisting of lower alkyl, lower alkoxy, cycloalkyl, aryloxy, aralkyloxy, optionally substituted aryloxy lower alkyl, optionally substituted aryloxycarbonyl, lower alkoxycarbonyl, nitro, hydroxy, carboxy, cyano, oxo, SO₂NH₂, SO₂Me, SO₂-cyclic amino, optionally substituted amino, optionally substituted carbamoyl, optionally substituted carbamoyloxy, halo, lower alkyl halide, lower alkoxy halide, lower alkylthio halide, lower alkylcarbonyl halide, heterocyclo lower alkyl, heterocyclo lower alkoxy, cycloalkyl lower alkoxy, aralkyloxy, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl, optionally substituted heteroaryl-lower alkyloxy, heterocycle, heterocycle lower alkyloxy, optionally substituted aryl, and optionally substituted heteroaryl;

(12) The compound of any one of (1) to (10) wherein Ar² is aryl that is optionally substituted with one or more of the substituent selected from the group consisting of halo, mono-, di- or tri-halogenated lower alkyl, mono-, di- or tri-halogenated lower alkoxy, mono-, di- or tri-halogenated lower alkylthio, mono- or di-lower alkylamino, cycloalkylmethyloxy, benzyloxy, lower alkoxycarbonylamino, nitro;

(13) The compound of any one of (1) to (12) wherein Ar¹ is phenyl optionally substituted with an optionally substituted amino;

(14) The compound of any one of (1) to (12) wherein Ar¹ is optionally substituted heteroaryl;

(15) The compound of any one of (1) to (12) wherein X¹ is lower alkylene; X² is a single bond, lower alkylene or a heteroatomic group as described above; X³ is a single bond, lower alkylene or heteroatomic group; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted heteroaryl; and Ar² is optionally substituted phenyl, optionally substituted heterocycle or optionally substituted cycloalkyl;

(16) The compound as described preferably in (1) or of any one of (3) to (15) wherein R^(B) is —OH; R^(C) is hydrogen; and R^(D) is hydrogen;

(17) The compound as described preferably in (1) or of any one of (3) to (15) wherein R^(B) is —NR⁵R⁵′ wherein R⁵ and R⁵′ are independently hydrogen, optionally substituted alkyl, —NH—R, —NH—COR, —NH—CONHR, —O—R wherein each R is independently hydrogen or optionally substituted alkyl, or amino sugar residue, R^(C) is hydrogen; and R^(D) is hydrogen;

(18) The compound as described preferably in (1) or any one of (3) to (15) wherein R^(B) is —NR⁵R⁵′ wherein R⁵ is hydrogen, R⁵′ is alkyl-NH—R, —NH—COR, —NH—CONHR, —O—R wherein each R is independently hydrogen or optionally substituted alkyl, or amino sugar residue, which are substituted with a hydrophilic substituent, R^(C) is hydrogen; and R^(D) is hydrogen.

The invention is also related to a compound as described above in (1) of the formula:

and a pharmaceutically acceptable salt or solvate thereof, wherein,

-   -   R^(A) is the formula —X¹—Ar¹—X²—Y—X³—Ar²         wherein, X¹, X² and X³ are independently         -   1) single bond;         -   2) heteroatom or heteroatomic group, selected from the group             consisting of —N═, ═N—, —NR¹—, —O—, —S—, —SO— and —SO₂—             wherein R¹ is hydrogen or lower alkyl; or         -   3) optionally substituted alkylene or alkenylene optionally             interrupted by one or more same or different heteroatomic             group;     -   Y is —NR²CO—, —CONR²— wherein R² is hydrogen or lower alkyl, or         a group represented by the formula:         wherein R³ is alkylene;     -   Ar¹ and Ar² are independently a carbocycle or heterocycle which         is optionally substituted and may have an unsaturated bond;     -   R^(B) is —OH or —NR⁵R⁵′ wherein R⁵ and R⁵′ are independently         hydrogen or optionally substituted alkyl;

R^(C) is hydrogen or optionally substituted alkyl that may comprise a heteroatomic group; and

R^(D) is hydrogen or lower alkyl.

The invention is also related to the compound represented by the formula of [formula 7] and a pharmaceutically acceptable salt or solvate thereof, wherein X¹ is lower alkylene; X² is a single bond or lower alkylene that may comprise a heteroatomic group; X³ is a single bond; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted phenyl; and Ar² is optionally substituted phenyl and R^(B) is OH, R^(C) and R^(D) are hydrogen.

EFFECT OF THE INVENTION

The glycopeptide antibiotic derivative of the invention, a pharmaceutically acceptable salt, or solvate thereof shows an antimicrobial activity against various microorganisms such as staphylococcus including MRSA, streptococcus, pneumococcus and enterococcus. The compound is also effective against vancomycin-resistant strains thereof, particularly vancomycin-resistant enterococcus (VRE) and vancomycin-resistant staphylococcus aureus (VRSA). Thus, the compound is useful in the treatment or prevention of various bacterial infectious diseases such as meningitis, sepsis, pneumonia, arthritis, peritonitis, bronchitis, empyema and the like. The more preferred compound of the invention is highly water-soluble and shows good pharmacokinetics and/or is safe with respect to toxicity.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

(1) Compound

In order to describe the compound of the invention, the terms as used herein have the following meaning solely or in combination with other terms as used herein.

The term “Glycopeptide antibiotic derivative aglycone part” refers to a moiety remaining after removal of a sugar moiety as described bellow, from a known glycopeptide antibiotic derivative characterized by polycyclic peptide core optionally substituted with a sugar group. One or more, preferably one “sugar moiety” may be removed. For example, in case that glycopeptide antibiotic derivative is vancomycin, the aglycone part is that remaining after the sugar chain (disaccharide) moiety containing an amino sugar (i.e. α-L-vancosaminyl-β-D-glucopyranose). Also, vancomycin derivatives having a modification at the N-terminal of the peptide chain, such as that having removal of the N-methyl-D-leucine and its acylated form, was known (Expert Opin. Ther. Patents (2004) 14, 141-173). Thus, the aglycone part includes such part of these vancomycin derivatives, from which “sugar moiety” has been removed as described above. Known glycopeptide antibiotic derivatives can be found in: Japanese Patent Publication 61-251699, Japanese Patent Publication 7-258289; WO96/30401; WO00/39156; Japanese Patent Publication 2000-302687; WO2004/44222; U.S. Pat. Nos. 4,639,433; 4,643,987; 4,497,802; 4,698,327; 5,591,714; 5,840,684; and 5,843,889; EP0802199; EP0801075; EP0667353; WO97/28812; WO97/38702; WO98/52589; WO98/52592; and J. Am. Chem. Soc., 1996, 118, 13107-13108; J. Am. Chem. Soc., 1997, 119, 12041-12047; and J. Am. Chem. Soc., 1994, 116, 4573-4590.

Specifically, the compound of the invention can be selected from the group consisting of the following compounds.

The compound of the formula:

or a pharmaceutically acceptable salt or solvate thereof, wherein,

R and R₁ is independently hydrogen or methyl;

R₂ and R₃ is independently hydrogen or, a group of the formula R₆R₇CH—, wherein R₆ and R₇ is independently R₅, R₅—(C₁-C₅)-alkyl or R₅— (C₂-C₅-alkenyl), wherein R₅ is hydrogen, C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₁-C₄-alkoxy, C₃-C₁₀-cycloalkyl, C₅-C₁₂-cycloalkenyl, phenyl, naphthyl, indenyl, tetralinyl, decalinyl, adamantyl, a monocyclic heteroring containing 3-8 heteroatoms or bicyclic heteroring containing 6-11 heteroatoms, with the proviso that at least one of these atoms is carbon, at least one of these heteroatoms is selected form O, N and S, and R₅ is optionally substituted with one or more selected from hydroxy, nitro, C₁-C₁₀-alkoxy, C₁-C₁₀-alkyl, phenyl, C₁-C₆-alkylthio, nitrile, halo, C₂-C₄-acylamino, amino, C₁-C₄-dialkylamino;

R₄ is hydrogen, or R₁ and R₂, and/or R₃ and R₄ together represent a group of the formula:

wherein R₆ and R₇ are R₅, R₅—(C₁-C₅-alkyl) or R₅—(C₂-C₅-alkenyl;

N is 1 or 2,

with the proviso that: (i) at least one of R₂ and R₃ is not hydrogen, (ii) when n is 2, then R is hydrogen, (iii) when R is methyl and R₃ is hydrogen, then R₂ is not methyl, (iv) when R and R₁ are both hydrogen, then R₂ is hydrogen or methyl and n is 1

(Japanese Patent Publication 61-251699).

The compound of the formula:

or a pharmaceutically acceptable salt or solvate thereof, wherein,

X and Y is independently hydrogen or chloro;

R is hydrogen, 4-epi-vancosaminyl, actinosaminyl or ristosaminyl;

R¹ is hydrogen or mannose;

R² is —NH₂, —NHCH₃ or —N(CH₃)₂;

R³ is —CH₂CH(CH₃)₂, [p-OH, m-Cl]phenyl, p-rhamnose-phenyl, [p-rhamnose-galactose]phenyl, [p-galactose-galactose]phenyl or [p-CH₃O-rhamnose]phenyl;

R⁴ is —CH₂ (CO)NH₂, benzyl, [p-OH]phenyl or [p-OH, m-Cl]phenyl;

R⁵ is hydrogen or mannose;

R⁶ is 4-epi-vancosaminyl, L-acosaminyl, L-ristosaminyl or L-actinosaminyl;

R⁷ is (C₂-C₁₆)alkenyl, (C₂-C₁₂)alkynyl, (C₁-C₁₂)alkyl-R⁸, (C₁-C₁₂-alkyl)-halo, (C₂-C₆-alkenyl)-R⁸, (C₂-C₆-alkynyl)-R⁸, (C₁-C₁₂-alkyl)-O—R⁸ and R⁷ connects to the amino group of R⁶;

R⁸ is

-   -   a) polycyclic aryl unsubstituted or substituted with one or more         independently selected from the group consisting of (i)         hydroxy, (ii) halo, (iii) nitro, (iv) (C₁-C₆)-alkyl, (v)         (C₁-C₆)-alkenyl, (vi) (C₁-C₆)-alkynyl, (vii) (C₁-C₆)-alkyl,         (C₁-C₆)-alkoxy, (viii) halo-(C₁-C₆)-alkyl, (ix)         halo-(C₁-C₆)-alkoxy, (x) carbo-(C₁-C₆)-alkoxy, (xi)         carbobenzyloxy, (xii) (C₁-C₆)-alkyl, (C₁-C₆)-carbobenzyloxy         substituted with alkoxy, halo or nitro, (xiii) a group of the         formula: —S(O)n′R⁹ wherein n′ is 0-2, R⁹ is (C₁-C₆)-alkyl,         phenyl or phenyl substituted with (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy,         halo or nitro, and (xiv) a group of the formula: —C(O)N(R¹⁰)₂         wherein R¹⁰ are independently hydrogen, (C₁-C₆)-alkyl,         (C₁-C₆)-alkoxy, phenyl, or phenyl substituted with         (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy, halo or nitro;     -   b) heteroaryl unsubstituted or substituted with one or more         selected independently from the group consisting of (i)         halo, (ii) (C₁-C₆)-alkyl, (iii) (C₁-C₆)-alkoxy, (iv)         halo-(C₁-C₆)-alkyl, (v) halo-(C₁-C₆)-alkoxy, (vi) phenyl, (vii)         thiophenyl, (viii) phenyl substituted with halo, (C₁-C₆)-alkyl,         (C₁-C₆)-alkenyl, (C₁-C₆)-alkynyl, (C₁-C₆)-alkoxy or nitro, (ix)         carbo-(C₁-C₆)alkoxy, (x) carbobenzyloxy, (xi) carbobenzyloxy         substituted with (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy halo or         nitro, (xii) a group of the formula: —S(O)n′R⁹ as defined         above, (xiii) a group of the formula: —C(O)N(R¹⁰)₂ as defined         above and (xiv) thienyl;     -   c) a group of the formula:         wherein,

A¹ is —OC(A2)₂—C(A2)₂—O—, —O—C(A²)₂-O—, —C(A²)₂-O— or —C(A²)₂-C(A²)₂-C(A²)₂-C(A²)₂-, wherein each A² is independently selected from hydrogen, (C₁-C₆)-alkyl, (C₁-C₆)alkoxy and (C₄-C₁₀)-cycloalkyl;

-   -   d) a group of the formula:         wherein,

p is 1 to 5, R¹¹ is selected independently form the group consisting of (i) hydrogen, (ii) nitro, (iii) hydroxy, (iv) halo, (v) (C₁-C₈)-alkyl, (vi) (C₁-C₆)-alkoxy, (vii) (C₉-C₁₂)-alkyl, (viii) (C₂-C₉)-alkynyl, (ix) (C₉-C₁₂)-alkoxy, (x) (C₁-C₃)-alkoxy, substituted with (C₁-C₃)-alkoxy, hydroxy, halo-(C₁-C₃)-alkoxy or (C₁-C₄)alkylthio, (xi) (C₂-C₅)-alkenyloxy, (xii) (C₁-C₁₃)-alkynyloxy, (xiii) halo-(C₁-C₆)-alkyl, (xiv) halo-(C₁-C₆)-alkoxy, (xv) (C₂-C₆)-alkylthio, (xvi) (C₂-C₁₀)-alkanoyloxy, (xvii) carboxy-(C₂-C₄)-alkenyl, (xviii) (C₁-C₃)-alkylsulfonyloxy, (xix) carboxy-(C₁-C₃)-alkyl, (xx) N-[di(C₁-C₃)alkyl]amino-(C₁-C₃)alkoxy, (xxi) cyano-(C₁-C₆)-alkoxy and (xxii) diphenyl-(C₁-C₆)-alkyl, with the proviso that: when R¹¹ is (C₁-C₈)-alkyl, (C₁-C₈)-alkoxy or halo, then P is 2 or more, and when R⁷ is (C₁-C₃-alkyl)-R⁸, then R¹¹ is not hydrogen, (C₁-C₈)-alkyl, (C₁-C₈)-alkoxy or halo;

-   -   e) a group of the formula:         wherein,

q is 0 to 4,

R¹² is selected independently from the group consisting of (i) halo, (ii) nitro, (iii) (C₁-C₆)-alkyl, (iv) (C₁-C₆)-alkoxy, (v) halo-(C₁-C₆)-alkyl, (vi) halo-(C₁-C₆)-alkoxy and (vii) hydroxy and (vii) (C₁-C₆)-thioalkyl, r is 1 to 5, with the proviso that q+r is not more than 5, Z is selected independently from the group consisting of (i) single bond, (ii) divalent (C₁-C₆)-alkyl, unsubstituted or substituted with hydroxy, (C₁-C₆)-alkyl or (C₁-C₆)-alkoxy, (iii) divalent (C₂-C₆)-alkenyl, (iv) divalent (C₂-C₆)-alkynyl, or (v) a group of the formula: —(C(R¹⁴)₂)s—R¹⁵— or —R¹⁵—(C(R¹⁴)₂)s—

wherein, S is 0-6, R¹⁴ are independently selected from hydrogen, (C₁-C₆)-alkyl or (C₄-C₁₀)-cycloalkyl, R¹⁵ is a group selected from —O—, —S—, —SO—, —SO₂—, —SO₂—O—, —C(O)—, —OC(O)—, —C(O)O—, —NH—, —N(C₁-C₆-alkyl)- and —C(O)NH—, —NHC(O)—, —N═N—,

R¹³ is selected independently from the group consisting of (i) (C₄-C₁₀)-heterocyclyl, (ii) heteroaryl, (iii) (C₄-C₁₀)-cycloalkyl unsubstituted or substituted with (C₁-C₆)-alkyl or (iv) phenyl unsubstituted or substituted with 1-5 substituents selected independently from the group consisting of halo, hydroxy, nitro, (C₁-C₁₀)-alkyl, (C₁-C₁₀)-alkoxy, halo-(C₁-C₃)-alkoxy, halo-(C₁-C₃)-alkyl, (C₁-C₃)-alkoxyphenyl, phenyl, phenyl-(C₁-C₃)-alkyl, (C₁-C₆)-alkoxyphenyl, phenyl-(C₁-C₃)-alkynyl and (C₁-C₆)-alkylphenyl;

-   -   f) (C₄-C₁₀)-cycloalkyl unsubstituted or substituted with one or         more selected independently from the group consisting of (i)         (C₁-C₆)-alkyl, (ii) (C₁-C₆)-alkoxy, (iii) (C₁-C₆)-alkenyl, (iv)         (C₁-C₆)-alkynyl, (v) (C₄-C₁₀)-cycloalkyl, (vi) phenyl, (vii)         phenylthio, (viii) phenyl substituted with nitro, halo,         (C₁-C₆)-alkanoyloxy or carbocycloalkoxy, and (ix) a group of the         formula: -Z—R¹³ wherein Z and R¹³ is as defined above;     -   g) a group of the formula:         wherein,

A³ and A⁴ are (i) a bond, (ii) —O—, (iii) —S(O)t— wherein t is 0 to 2, (iv) —C(R¹⁷)₂— wherein R¹⁷ is independently selected from hydrogen, (C₁-C₆)-alkyl, hydroxy, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy, or both R¹⁷s together represent O, (v) —N(R¹⁸)₂— wherein R¹⁸ is independently selected from hydrogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkenyl, (C₁-C₆)-alkynyl, (C₄-C₁₀)-cycloalkyl, phenyl, or phenyl substituted with nitro, halo or (C₁-C₆)-alkanoyloxy, or both R^(18s) together represent (C₄-C₁₀)-cycloalkyl,

R¹⁶ is R¹² or R¹³ as defined above, and

u is 0-4.

The compound of the formulae (1) and (2):

wherein,

n is an integer from 0 to 10,

n′ is an integer from 1 to 12, and

m is an integer from 2 to 60

(Japanese Patent Publication 2000-302687); or

The compound of the formula I:

and a pharmaceutically acceptable salt, stereoisomer and prodrug thereof, wherein,

R¹ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic ring and —R^(a)—Y—R^(b)-(Z)_(x); or a saccharide group optionally substituted with —R^(a)—Y—R^(b)-(Z)_(x);

R² is hydrogen, or a saccharide group optionally substituted with —R^(a)—Y—R^(b) (Z)_(x);

R³ is —OR^(c) or —NR^(c)R^(c);

R⁴ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —R^(a)—Y—R^(b)-(Z)_(x), —C(O)R^(d) and a saccharide group optionally substituted with —R^(a)—Y—R^(b)-(Z)_(x);

R⁵ is selected from the group consisting of hydrogen, halo, —CH(R^(c))—NR^(c)R^(c), —CH(R^(c))—NR^(c)R^(e) and —CH(R^(c))—NR^(c)—R^(a)—Y—R^(b)-(Z)_(x);

R⁶ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —R^(a)—Y—R^(b)-(Z)_(x), —C(O)R^(d) and a saccharide group optionally substituted with —NR^(c)—R^(a)—Y—R^(b)-(Z)_(x), or R⁵ and R⁶ together with the atom to which they are attached to form a heterocyclic ring optionally substituted with —NR^(c)—R^(a)—Y—R^(b)-(Z)_(x);

R⁷ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —R^(a)—Y—R^(b)(Z)_(x), and —C(O)R^(d);

R⁸ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring;

R⁹ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring;

R¹⁰ is selected from the group consisting of alkyl and substituted alkyl;

R¹¹ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring, or R¹⁰ and R¹¹ together with the carbon and nitrogen atoms to which they are attached to form a heterocyclic ring;

R¹² is selected from the group consisting of hydrogen, alkyl, substituted alkyl and —C(O)OR^(d);

R¹³ is selected from the group consisting of hydrogen or —OR¹⁴;

R¹⁴ is selected from the group consisting of hydrogen, —C(O)R^(d) and a saccharide group;

R^(a) is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;

R^(b) is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;

R^(c) is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic ring and —C(O)R^(d)

R^(d) is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring;

R^(e) is a saccharide group;

X¹, X² and X³ are selected from the group consisting of hydrogen or chloro;

Y is selected independently from the group consisting of oxygen, sulphur, —S—S—, —NR^(c)—, —S(O)—, —SO₂—, —NR^(c)C(O)—, —OSO₂—, —OC(O)—, —NR^(c)SO₂—, —C(O)NR^(c)—, —C(O)O—, —SO₂NR^(c)—, —SO₂O—, —P(O) (OR^(c)) O—, —P(O) (OR^(c)) NR^(c)—, —OP(O)(OR^(c)) O—, —OP(O)(OR^(c))NR^(c)—, —OC(O)O—, —NR^(C)C(O)O—, —NR^(C)C(O)NR^(c)—, —OC(O)NR^(C)— and —NR^(C)SO₂NR^(c)—;

Z is selected independently from the group consisting of hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic ring;

n is, 0, 1 or 2; and

X is 1 or 2,

with the proviso that at least one of R¹, R², R⁴R⁵, R⁶ or R⁷ is a group of the formula —R^(a)—Y—R^(b)-(Z)_(x); and further that

(i) when Y is —NR^(C)—, R^(C) is 1 to 4 carbon alkyl, Z is hydrogen, and R^(b) is alkylene, then R^(b) contains at least five carbon atoms;

(ii) when Y is —C(O)NR^(c)—, Z is hydrogen, and R^(b) is alkylene, then R^(b) is at least five carbon atoms;

(iii) when Y is sulphur, Z is hydrogen, and R^(b) is alkylene, then R^(b) is at least seven carbon atoms; and

(iv) when Y is oxygen, Z is hydrogen, and R^(b) is alkylene, then R^(b) is at least eleven carbon atoms

(Japanese Patent Publication 2002-533472).

The compound of the formula I:

and a pharmaceutically acceptable salt, stereoisomer and prodrug thereof, wherein,

R¹ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic ring and —R^(a)—Y—R^(b)-(Z)_(x), or R¹ is a saccharide group optionally substituted with —R^(a)—Y—R^(b)-(Z)_(x), R^(f), —C(O)R^(f) or —C(O)—R^(a)—Y—R^(b)-(Z)_(x);

R² is hydrogen, or a saccharide group optionally substituted with —R^(a)—Y—R^(b)—(Z)_(x), R^(f), —C(O)R^(f) or —C(O)—R^(a)—Y—R^(b)-(Z)_(x);

R³ is —OR^(c), —NR^(c)R^(c), —O—R^(a)—Y—R^(b)—(Z)_(x), —NR^(c)—R^(a)—Y—R^(b)—(Z)_(x), —NR^(C)R^(e), or —O—R^(e), or R³ is a N-, O- or S-linked group containing one or more phosphono moiety;

R⁴ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —R^(a)—Y—R^(b)—(Z)_(x), —C(O)R^(d) and —R^(a)—Y—R^(b)—(Z)_(x), R^(f), —C(O)R^(f) or a saccharide group optionally substituted with —C(O)—R^(a)—Y—R^(b)—(Z)_(x):

R⁵ is selected from the group consisting of hydrogen, halo, —CH(R^(c))—NR^(c)R^(c), —CH(R^(c))—NR^(C)R^(e), —CH(R^(C))—NR^(c)—R^(a)—Y—R^(b)—(Z)_(x), —CH(R^(C))—Rx, —CH(R^(c))—NR^(c)—R^(a)—C(═O)—R_(x) and a group containing one or more phosphono moiety;

R⁶ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —R^(a)—Y—R^(b)—(Z)_(x), —C(O)R^(d) and a saccharide group optionally substituted with —NR^(c)—R^(a)—Y—R^(b)-(Z)_(x), or R⁵ and R⁶ together with the atom to which they are attached to form a heterocyclic ring optionally substituted with —NR^(C)—R^(a)—Y—R^(b)—(Z)_(x);

R⁷ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —R^(a)—Y—R^(b)—(Z)_(x) and —C(O)R^(d);

R⁸ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring;

R⁹ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring;

R¹⁰ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring; or R^(B) and R¹⁰ together form —Ar¹⁰—O—Ar²— wherein, Ar¹ and Ar² are independently arylene or heteroarylene;

R¹¹ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring, or R¹⁰ and R¹¹ together with the carbon atom and nitrogen atom to which they are attached to form a heterocyclic ring;

R¹² is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic ring, —C(O)R^(d), —C(NH)R^(d), —C(O)NR^(C)R^(c), —C(O)OR^(d), C(NH)NR^(C)R^(c) and —R^(a)—Y—R^(b)—(Z)_(x), or R¹¹ and R¹² together with the nitrogen atom to which they are attached to form a heterocyclic ring;

R¹³ is selected from the group consisting of hydrogen or —OR¹⁴;

R¹⁴ is selected from the group consisting of hydrogen, —C(O)R^(d) and a saccharide group;

R^(a) is selected independently from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;

R^(b) is selected independently from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, with the proviso that: R^(b) is not covalent bond when Z is hydrogen;

R^(c) is selected independently from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic ring and —C(O)R^(d);

R^(d) is selected independently from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic ring;

R^(e) is a saccharide group;

R^(f) is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl or heterocyclic ring;

R^(X) is N-linked aminosaccharide or N-linked heterocyclic ring, and X¹, X² and X³ are selected independently from hydrogen or chlorine;

Y is selected independently from the group consisting of oxygen, sulphur, —S—S—, —NR^(C)—, —S(O)—, —SO₂—, —NR^(C)C(O)—, —OSO₂—, —OC(O)—, —NR^(c)SO₂—, —C(O)NR^(c)—, —C(O)O—, —SO₂NR^(c)—, —SO₂O—, —P(O)(OR^(c))O—, —P(O)(OR^(c))NR^(c)—, —OP(O)(OR^(c))O—, —OP(O)(OR^(c))NR^(c)—, —OC(O)O—, —NR^(C)C(O)O—, NR^(C)C(O)NR^(c)—, —OC(O)NR^(c)—, —C(═O)— and —NR^(c)SO₂NR^(c)—;

Z is selected independently from hydrogen, aryl; cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic ring;

n is 0, 1 or 2; and

x is 1 or 2

(Japanese Patent Publication 200 3-531869).

The glycopeptide of the formula: A₁−A₂−A₃−A₄−A₅−A₆−A₇ and a pharmaceutically acceptable salts thereof, wherein,

each dash represents a covalent bond;

the group A₁ comprises a modified or unmodified alpha-amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocycle, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl;

each of the groups A₂ to A₇ comprises a modified or unmodified alpha-amino acid residue, whereby (i) the group A₁ is linked to an amino group on the group A₂, (ii) each of the groups A₂, A₄ and A6 bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A₇ bears a terminal carboxyl, ester, amide, or N-substituted amide group; and

one or more of the groups A₁ to A₇ is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues; wherein at least one of said sugar residues is a disaccharide modified to bear one or more substituents of the formula: YXR, N⁺ (R₁)═CR₂R₃, N═PR₁R₂R₃, N⁺R₁R₂R₃ or P⁺R₁R₂R₃ in which the group Y is a single bond, O, NR₁, or S; the group X is O, NR₁, S, SO₂, C(O)O, C(O)S, C(S)O, C(S)S, C(NR₁)O, C(O)NR₁, or halo (in which case Y and R are absent); and R, R₁, R₂, and R₃ are independently hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl;

with the proviso that at least one of the substituents of the formula YXR is not hydroxyl; X and Y are not both O; X and Y are not S and O, or O and S, respectively; and if two or more of said substituents are present, they can be the same or different; and with the proviso that when A₄ is linked to a disaccharide having a glucose residue that bears an N-substituted aminohexose residue, then said glucose residue is modified to bear at least one of said substituents YXR, N⁺ (R₁)═CR₂R₃, N═PR₁R₂R₃, N⁺R₁R₂R₃ or P⁺R₁R₂R₃ (Japanese Patent Publication 2002-520422).

The compound of the formula:

or salt thereof, wherein:

X is hydrogen or chloro;

R is 4-epi-vancosaminyl or a group of the formula —R^(a)-R^(7a), wherein R^(a) is 4-epi-vancosaminyl and R^(7a), defined below, is attached to the amino group of R^(a);

R² is —NHCH₃ or —N(CH₃)R^(7b), wherein R^(7b) is defined below;

R⁶ is 4-epi-vancosaminyl;

R⁷ is as defined below, is attached to the amino group of R⁶; and

R⁷, R^(7a) and R^(7b) are each independently selected from the group consisting of hydrogen, C₂₋₁₆alkenyl, C₂₋₁₂alkynyl, (C₁₋₁₂alkyl)-R⁸, (C₁₋₁₂alkyl)-halo, (C₂₋₆alkenyl)-R⁸, (C₂₋₆alkynyl)-R⁸ and (C₁₋₁₂alkyl)-O—R⁸, with the proviso that R⁷, R^(7a) and R^(7b) are not all hydrogen, and R⁸ is selected from the group consisting of

a) multicyclic aryl unsubstituted or substituted with one or more substituents independently selected from the group consisting of:

(i) hydroxy,

(ii) halo,

(iii) nitro,

(iv) C₁₋₆alkyl,

(v) C₁₋₆alkenyl,

(vi) C₁₋₆alkynyl,

(vii) C₁₋₆alkoxy,

(viii) halo-(C₁₋₆alkyl),

(ix) halo-(C₁₋₆alkoxy),

(x) carbo-(C₁₋₆alkoxy),

(xi) carbobenzyloxy,

(xii) carbobenzyloxy substituted with C₁₋₆alkyl, C₁₋₆alkoxy, halo or nitro,

(xiii) a group of the formula —S(O)n′—R⁹ wherein n′ is 0-2 and R⁹ is C₁₋₆alkyl, phenyl or phenyl substituted with C₁₋₆alkyl, C₁₋₆alkoxy, halo, or nitro and

(xiv) a group of the formula —C(O)N(R¹⁰)₂ wherein each R¹⁰ substituent is independently hydrogen, C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, or phenyl substituted with C₁₋₆ alkyl, C₁₋₆alkoxy, halo, or nitro;

-   -   b) heteroaryl unsubstituted or substituted with one or more         substituents independently selected from the group consisting         of:

(i) halo,

(ii) C₁₋₆alkyl,

(iii) C₁₋₆alkoxy,

(iv) halo-(C₁₋₆alkyl),

(v) halo-(C₁₋₆alkoxy),

(vi) phenyl,

(vii) thiophenyl,

(viii) phenyl substituted with halo, C₁₋₆alkyl, C₁₋₆alkenyl, C₁₋₆alkynyl, C₁₋₆alkoxy, or nitro,

(ix) carbo-(C₁₋₆alkoxy),

(x) carbobenzyloxy,

(xi) carbobenzyloxy substituted with C₁₋₆alkyl, C₁₋₆alkoxy, halo or nitro,

(xii) a group of the formula —S(O)n′—R⁹ as defined above,

(xiii) a group of the formula —C(O)N(R¹⁰)₂ as defined above, and

(xiv) thienyl;

-   -   c) a group of the formula:         wherein A¹ is —OC(A2)₂C(A2)₂O—, —OC(A2)₂O—, —C(A2)₂O— or         —C(A2)₂C(A2)₂C(A2)₂C(A2)₂—, and each A² substituent is         independently selected from hydrogen, C₁₋₆alkyl, C₁₋₆alkoxy and         C₄₋₁₀cycloalkyl;     -   d) a group of the formula:         wherein

p is from 1 to 5; and

R¹¹ is independently selected from the group consisting of:

(i) hydrogen,

(ii) nitro,

(iii) hydroxy,

(iv) halo

(v) C₁₋₈alkyl,

(vi) C₁₋₈alkoxy,

(vii) C₉₋₁₂alkyl,

(viii) C₂₋₉alkynyl,

(ix) C₉₋₁₂alkoxy,

(x) C₁₋₃alkoxy substituted with C₁₋₃alkoxy, hydroxy, halo-C₁₋₃alkoxy or C₁₋₄alkylthio,

(xi) C₂₋₅alkenyloxy,

(xii) C₁₋₁₃alkynyloxy,

(xiii) halo-C₁₋₆alkyl,

(xiv) halo-C₁₋₆alkoxy,

(xv) C₂₋₆alkylthio,

(xvi) C₂₋₁₀alkanoyloxy,

(xvii) carboxy-(C₂₋₄alkenyl),

(xviii) C₁₋₃alkylsulfonyloxy,

(xix) carboxy-(C₁₋₃alkyl),

(xx) N-[di(C₁₋₃alkyl]amino-(C₁₋₃alkoxy),

(xxi) cyano-(C₁₋₆alkoxy) and

(xxii) diphenyl-(C₁₋₆alkyl),

with the proviso that when R¹¹ is C₁₋₉alkyl, C₁₋₈alkoxy or halo, p must be greater or equal to 2, or when R⁷ is C₁₋₃alkyl-R⁸ then R¹¹ is not hydrogen, C₁₋₉alkyl, C₁₋₈alkoxy or halo;

-   -   e) a group of the formula:         wherein

q is 0 to 4;

R¹² is independently selected from the group consisting of:

(i) halo,

(ii) nitro,

(iii) C₁₋₆alkyl,

(iv) C₁₋₆alkoxy,

(v) halo-(C₁₋₆alkyl),

(vi) halo-(C₁₋₆alkoxy),

(vii) hydroxy and

(viii) C₁₋₆thioalkyl,

-   -   r is 1 to 5; with the proviso that the sum of q and r is no         greater than 5;     -   Z is selected from the group consisting of:

(i) single bond,

(ii) divalent C₁₋₆alkyl unsubstituted or substituted with hydroxy, C₁₋₆alkyl, or C₁₋₆alkoxy,

(iii) divalent C₂₋₆alkenyl,

(iv) divalent C₂₋₆alkynyl, or

(v) a group of the formula —(C(R¹⁴)₂)sR¹⁵— or —R¹⁵ (C(R¹⁴)₂)s—, wherein s is 0-6, wherein each R¹⁴ substituent is independently selected from hydrogen, C₁₋₆alkyl or C₄₋₁₀cycloalkyl, and R¹⁵ is selected from —O—, —S—, —SO—, —SO₂—, —SO₂O—, —C(O)—, —OC(O)—, —C(O)O—, —NH—, —N(C₁₋₆alkyl)-, —C(O)NH—, —NHC(O)— and —N═N—;

R¹³ is independently selected from the group consisting of:

(i) C₄₋₁₀heterocycle,

(ii) heteroaryl,

(iii) C₄₋₁₀cycloalkyl unsubstituted or substituted with C₁₋₆alkyl or

(iv) phenyl unsubstituted or substituted with 1 to 5 substituents independently selected from: halo, hydroxy, nitro, C₁₋₁₀alkyl, C₁₋₁₀alkoxy, halo-C₁₋₃alkoxy, halo-C₁₋₃alkyl, C₁₋₃alkoxyphenyl, phenyl, phenyl-(C₁₋₃alkyl), C₁₋₆alkoxyphenyl, phenyl-(C₁₋₃alkynyl) and C₁₋₆alkylphenyl;

f) C₄₋₁₀cycloalkyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of:

(i) C₁₋₆alkyl,

(ii) C₁₋₆alkoxy,

(iii) C₁₋₆alkenyl,

(iv) C₁₋₆alkynyl,

(v) C₄₋₁₀cycloalkyl,

(vi) phenyl,

(vii) phenylthio,

(viii) phenyl substituted with nitro, halo, C₁₋₆alkanoyloxy or carbocycloalkoxy and

(ix) a group represented by the formula -ZR¹³ wherein Z and R¹³ is as defined above; and

-   -   g) a group of the formula:         wherein

A³ and A⁴ are each independently selected from

(i) a bond,

(ii) —O—,

(iii) —S(O)t—, wherein t is 0 to 2,

(iv) —C(R¹⁷)₂—, wherein each R¹⁷ substituent is independently selected from hydrogen, C₁₋₆alkyl, hydroxy and C₁₋₆alkoxy, or both R¹⁷ substituents taken together are O,

(v) —N(R¹⁸)₂—, wherein each R¹⁸ substituent is independently selected from hydrogen, C₁₋₆alkyl, C₁₋₆alkenyl, C₁₋₆alkynyl, C₄₋₁₀cycloalkyl, phenyl, phenyl substituted with nitro, halo, C₁₋₆alkanoyloxy or both R¹⁸ substituents taken together are C₄₋₁₀cycloalkyl;

-   -   R¹⁶ is R¹² or R¹³ as defined above: and     -   u is 0-4,         excluding compounds wherein R is 4-epi-vancosaminyl and R² is         —NH(CH₃)         (Japanese Patent Publication 1 1-502534).

Examples of the glycopeptide antibiotic derivatives are for example, vancomycin, teicoplanin, ristomycin, ristocetin, actaplanin, actinoidin, ardacin, avoparcin, azureomycin, balhimycin, chloroorienticin A, chloroorienticin B, chloropolysporin, decaplanin, N-demethylvancomycin, eremomycin, galacardin, helvecardin, izupeptin, kibdelin, mannopeptin, orienticin, parvodicin, synmonicin, oritavancin, telavancin, dalbavancin, A-40926, etc.

The term “sugar moiety” refers to a monosaccharide or a polysaccharide (e.g., disaccharide) moiety, and includes amino sugar, a sugar chain moiety containing amino sugar, or other sugar or sugar chain moieties. Amino sugar moiety or sugar chain (preferably disaccharide) containing amino sugar moiety is preferred, for example, in case of vancomycin, disaccharide attached to the phenol moiety, i.e., α-L-vancosaminyl-β-D-glucopyranose moiety. The sugar moiety typically includes, for example, D-glucose, D-mannose, D-xylose, D-galactose, vancosamin, 3-desmethylvancosamin, 3-epi-vancosamin, 4-epi-vancosamin, acosamin, actinosamin, daunosamin, 3-epi-daunosamin, ristosamin, N-methyl-D-glucamin, D-glucuronic acid, N-Acetyl-D-glucosamin, N-Acetyl-D-galactosamine, sialic acid, 2-O-(α-L-vancosaminyl)-p-β-glucopyranose, 2-O-(3-desmethyl-α-L-vancosaminyl)-β-D-glucopyranose, sucrose, lactose, or maltose.

The term “sugar residue” refers to a residual moiety of the above “sugar moiety” from which one OH has been removed.

The term “amino sugar residue” refers to a residual moiety of the “amino sugar” or “a sugar chain moiety containing amino sugar” from which one amino group has been removed.

The term “Sac-NH” moiety refers to an amino sugar moiety or a sugar chain moiety containing amino sugar as known in glycopeptide antibiotic derivatives. The term “amino sugar moiety” refers to a monosaccharide group having an amino group or a substituted amino group. Typical amino sugar moiety includes L-vancosaminyl, 3-desmethyl-vancosaminyl, 3-epi-vancosaminyl, 4-epi-vancosaminyl, 4-keto-vancosaminyl, acosaminyl, actinosaminyl, daunosaminyl, 3-epi-daunosaminyl, ristosaminyl, N-methyl-D-glucaminyl, N-Acetyl-D-glucosamyl, or N-acyl-D-glucosamyl, etc. Actinosaminyl, acosaminyl, 4-epi-vancosaminyl, 4-keto-vancosaminyl, ristosaminyl, or vancosaminyl is preferred. Particularly, L-vancosaminyl is preferred. Also, α-L-vancosaminyl-β-D-glucopyranose, 3-desmethyl-α-L-vancosaminyl-β-D-glucopyranose can be exemplified for a sugar chain moiety containing amino sugar.

As described above, “(aglycon part of glycopeptide antibiotic derivative)-(Sac-NH)” is a glycopeptide antibiotic derivative having a terminal amino sugar moiety.

Thus, glycopeptide antibiotic derivatives of the invention is a compound having R^(A) group attached to the amino group of the terminal amino sugar.

R^(A) is represented by the formula: —X¹—Ar¹—X¹—Y—X³—Ar². R^(A) group is characterized in that Y moiety comprises an amide bond.

The term “lower alkyl” refers to a saturated straight or branched hydrocarbon mono radical having 1 to 6 carbons, and includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, N-hexyl, isohexyl.

The term “linking group” in the definition for X¹, X² and X³ refers to a linking group that comprises a hetero atom selected from the group consisting of —N═, ═N—, —NR¹— (wherein R¹ is hydrogen or lower alkyl), —O—, —S—, —SO— and —SO₂— selected from the group, and includes for example —S—S—, —NR¹CO—, —NR¹O—, —NR¹S—, —OSO₂—, —OCO—, —SO₂NR¹—, etc.

The term “alkylene” refers to a saturated straight or branched hydrocarbon diradical having 1 to 6 carbons, and includes for example methylene, ethylene, trimethylene, propylene, tetramethylene, ethylethylene, pentamethylene or hexamethylene, etc. A saturated straight or branched alkylene having one to four carbon atoms, such as methylene, ethylene, trimethylene or tetramethylene is preferred. Preferred is methylene.

The term “alkenylene” refers to an unsaturated straight or branched hydrocarbon diradical of 2 to 6 carbons, having one or more double bond in the above “alkylene”, and includes for example vinylene, propenylene or butenylene. A straight chain alkenylene of 2 or 3 carbons, such as vinylene or propenylene, is preferred.

The term “optionally substituted alkylene or alkenylene” refers to alkylene or alkenylene having 1 to 5 substituents, preferably 1 to 3 substituents, wherein said substituent is selected from the group consisting of: optionally substituted alkyl (e.g., methyl, ethyl, isopropyl, benzyl, carbamoylalkyl (e.g., carbamoylmethyl), mono- or di-alkylcarbamoylalkyl (e.g., dimethylcarbamoylethyl), hydroxyalkyl, heterocyclealkyl (e.g., morpholinoethyl, tetrahydropyranylethyl), alkoxycarbonylalkyl (e.g., ethoxycarbonylmethyl, ethoxycarbonylethyl), mono- or di-alkylaminoalkyl (e.g., dimethylamminioethyl) etc), alkoxyalkyl (e.g., methoxyethyl, ethoxymethyl, ethoxyethyl, i-propoxyethyl etc), acyl (e.g., formyl, optionally substituted alkylcarbonyl (e.g., acetyl, Propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, octanoyl, methoxyethylcarbonyl, 2,2,2-trifluoroethylcarbonyl, ethoxycarbonylmethylcarbonyl, alkoxyalkylcarbonyl (e.g., methoxyethylcarbonyl), alkylcarbamoylalkylcarbonyl (e.g., methylcarbamoylethylcarbonyl), alkoxycarbonylacetyl etc), optionally substituted arylcarbonyl (e.g., benzoyl, toluoyl etc)), optionally substituted aralkyl (e.g., benzyl, 4-F-benzyl etc), hydroxy, optionally substituted alkylsulfonyl (e.g., methanesulfonyl, ethanesulphonyl, isopropylsulphonyl, 2,2,2-trifluoroethanesulphonyl, benzylsulphonyl, methoxyethylsulphonyl etc), arylsulfonyl optionally substituted with alkyl or halo (e.g., benzenesulfonyl, toluenesulfonyl, 4-fluorobenzenesulfonyl), cycloalkyl (e.g., cyclopropyl etc), aryl optionally substituted with alkyl (e.g., 4-methylphenyl etc), alkylaminosulphonyl (e.g., methylaminosulphonyl, dimethylamminiosulphonyl etc), alkylaminocarbonyl (e.g., dimethylaminocarbonyl etc), alkoxycarbonyl (e.g., ethoxycarbonyl etc), cycloalkylcarbonyl (e.g., cyclopropylcarbonyl, cyclohexylcarbonyl etc), optionally substituted sulfamoyl (e.g., sulfamoyl, methylsulfamoyl, dimethylsulfamoyl etc), alkylcarbonylamino (e.g., methylcarbonylamino), heterocycle (e.g., morpholino, tetrahydropyranyl), optionally substituted amino (e.g., mono- or di-alkylamino (such as dimethylamminio), formylamino).

Thus, “optionally substituted alkylene or alkenylene optionally interrupted by one or more same or different heteroatomic group” refers to alkylene or alkenylene optionally substituted and optionally interrupted by one or more same or different of a heteroatomic group selected from the group consisting of —N═, ═N—, —NR¹— wherein R¹ is hydrogen or lower alkyl, —O—, —S—, —SO— and —SO₂—. In this regard, “interrupted” means the presence of a heteroatomic group between carbon atoms composing such alkylene or alkenylene or between said carbon atom and Ar¹, Y or Ar². For example, —O—CH₂—, —CH₂—O—, —CH₂—O—CH₂—, CH₂—NH—CH₂—, —O—CH₂—O—, —CH₂—O—CH₂—NH—CH₂—, CH₂—N═CH—, —CH₂—O—CH═N—CH₂—, and —O—CH═CH—, —CH═CH—O—, —CH═CH—O—CH₂—, CH₂—NH—CH═CH—, —O—CH═CH—O—, or —(CH₂—O)—Ar¹—(O—CH₂—O)—Y—(O—CH₂)—Ar2, etc. are exemplified. Also, in the case that alkylene is substituted with oxo, —CO— is preferably exemplified.

X¹ is preferably C₁-C₃ alkylene.

X² is preferably a single bond, C₁-C₃ alkylene, O or NH, more preferably, single bond or NH.

Y is preferably, —NHCO—, —CONH—, —NMeCO—, —CONMe— or a radical as follows:

Also, Y is may be a piperazine ring group, and more preferably, —NHCO— or —CONH—.

X³ is preferably a single bond, C₁-C₃ alkylene, O or NH, more preferably a single bond.

Also, —Y—X³— and —X²—Y— may form a structure of the formula:

Ar¹ and Ar² are each a carbocycle or a heterocycle that may be substituted or unsaturated.

The term “optionally unsaturated carbocycle” in the definition for Ar¹ and Ar² refers to a cycloalkyl of 3-10 carbon or a cycloalkenyl or aryl of 3-10 carbon.

The term “cycloalkyl” includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexylyl, cycloheptyl, cyclooctyl, etc. Cycloalkyl of 3-6 carbon atoms, such as cyclopentyl, cyclohexylyl, is preferred.

The term “cycloalkenyl” includes, for example, cyclopropenyl (e.g., 1-cyclopropenyl), cyclobutenyl (e.g., 1-cyclobutenyl), cyclopentenyl (e.g., 1-cyclopentene-1-yl, 2-cyclopentene-1-yl, 3-cyclopentene-1-yl), cyclohexenyl (e.g., 1-cyclohexene-1-yl, 2-cyclohexene-1-yl, 3-cyclohexene-1-yl), cycloheptenyl (e.g., 1-cycloheptenyl), cyclooctenyl (e.g., 1-cyclooctenyl). Particularly, 1-cyclohexene-1-yl, 2-cyclohexene-1-yl, 3-cyclohexene-1-yl are preferred.

The term “aryl” refers to a monocyclic aromatic hydrocarbon group (phenyl) and a polycyclic aromatic hydrocarbon group (e.g., 1-naphythyl, 2-naphythyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl, 9-phenanthryl etc). Phenyl or naphythyl (e.g., 1-naphythyl, 2-naphythyl) is preferred.

The term “optionally unsaturated heterocycle” in the definition for Ar¹ and Ar² means a heterocycle or a heteroaryl.

The term “heterocycle” refers to a nonaromatic heterocyclic group having at least one N, O or S atom within the ring, the ring being optionally substituted at a substitutable position. Examples are 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, 1-pyrrolindinyl, 2-pyrrolindinyl, 3-pyrrolindinyl, 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1-pyrazolynyl, 3-pyrazolynyl, 4-pyrazolynyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, piperidino, 2-piperidyl, 3-piperidyl, 4-piperidyl, 1-piperazinyl, 2-piperazinyl, 2-morpholinyl, 3-morpholinyl, morpholino, tetrahydropyranyl etc. The “a nonaromatic heterocyclic group” may be saturated or unsaturated so long as it is not aromatic.

The term “heteroaryl” refers to a monocyclic aromatic heterocyclic group and a condensed aromatic heterocyclic group. The monocyclic aromatic heterocyclic group is that optionally substituted at a substitutable position and derived from a 5-8 membered aromatic ring that may contain one to four O, S, and/or N atom within the ring. The condensed aromatic heterocyclic group is that optionally substituted at a substitutable position and wherein a 5-8 membered aromatic ring containing one to four O, S, and/or N atom within the ring is condensed with one to four 5-8 membered aromatic carbocycles or another 5-8 membered aromatic hetero ring.

The “heteroaryl” includes, for example, furyl (e.g., 2-furyl, 3-furyl), thienyl (e.g., 2-thienyl, 3-thienyl), pyrrolyl (e.g., 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), imidazolyl (e.g., 1-imidazolyl, 2-imidazolyl, 4-imidazolyl), pyrazolyl (e.g., 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), triazolyl (e.g., 1,2,4-triazol-1-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-4-yl), tetrazolyl (e.g., 1-tetrazolyl, 2-tetrazolyl, 5-tetrazolyl), oxazolyl (e.g., 2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isoxazolyl (e.g., 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), thiazolyl (e.g., 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), thiadiazolyl, isothiazolyl (e.g., 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyridazinyl (e.g., 3-pyridazinyl, 4-pyridazinyl), pyrimidinyl (e.g., 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl), furazanyl (e.g., 3-furazanyl), pyrazinyl (e.g., 2-pyrazinyl), oxadiazolyl (e.g., 1,3,4-oxadiazole-2-yl), benzofuryl (e.g., 2-benzo[b]furyl, 3-benzo[b]furyl, 4-benzo[b]furyl, 5-benzo[b]furyl, 6-benzo[b]furyl, 7-benzo[b]furyl), benzthienyl (e.g., 2-benzo[b]thienyl, 3-benzo[b]thienyl, 4-benzo[b]thienyl, 5-benzo[b]thienyl, 6-benzo[b]thienyl, 7-benzo[b]thienyl), benzimidazolyl (e.g., 1-benzoimidazolyl, 2-benzoimidazolyl, 4-benzoimidazolyl, 5-benzoimidazolyl), dibenzofuryl, benzoxazolyl, quinoxalyl (e.g., 2-quinoxalinyl, 5-quinoxalinyl, 6-quinoxalinyl), cinnolinyl (e.g., 3-cinnolinyl, 4-cinnolinyl, 5-cinnolinyl, 6-cinnolinyl, 7-cinnolinyl, 8-cinnolinyl), quinazolyl (e.g., 2-quinazolinyl, 4-quinazolinyl, 5-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl, 8-quinazolinyl), quinolyl (e.g., 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), phthalazinyl (e.g., 1-phthalazinyl, 5-phthalazinyl, 6-phthalazinyl), isoquinolyl (e.g., 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), puryl, pteridinyl (e.g., 2-pteridinyl, 4-pteridinyl, 6-pteridinyl, 7-pteridinyl), carbazolyl, phenanthridinyl, acridinyl (e.g., 1-acridinyl, 2-acridinyl, 3-acridinyl, 4-acridinyl, 9-acridinyl), indolyl (e.g., 1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), isoindolyl, phenazinyl (e.g., 1-phenazinyl, 2-phenazinyl) or phenanthridinyl (e.g., 1-phenanthridinyl, 2-phenanthridinyl, 3-phenanthridinyl, 4-phenanthridinyl), etc.

The carbocycle and/or heterocycle in Ar₁ and Ar₂ also include those wherein an aromatic ring is condensed with a nonaromatic ring.

As obvious from the definition of R^(A), which is a divalent group, a carbon atom or a hetero atom within the carbocycle or heterocycle, described above as a monovalent group in R^(A), should involve in a linkage to another group.

Preferred R^(A) is a divalent ring group as follows:

Particularly, phenylenes, such as 1,2-, 1,3-, and 1,4-phenylene, are preferred. Also, preferred embodiment of the heterocycle group includes a five or six membered ring containing one to two N atom.

Ar² may be selected form the following groups:

Ar² is preferably an optionally substituted aryl, particularly preferably an optionally substituted phenyl.

Substituent for “a carbocycle or heterocycle which is optionally substituted and may have an unsaturated bond” in the definition for Ar¹ and Ar² include lower alkyl, hydroxy lower alkyl, optionally substituted lower alkoxy (for example: hydroxy, phenyloxy, optionally substituted heterocycle (preferably 5-6 membered ring), lower alkoxy, optionally substituted amino (for example, lower alkyl, lower alkenyl, cyano, phenyl), optionally substituted lower alkoxy lower alkyl (for example: hydroxy, lower alkoxy, optionally substituted heterocycle (preferably 5-6 membered ring)), cycloalkyl, optionally substituted aryloxy, optionally substituted aralkyloxy, optionally substituted aryloxy lower alkyl, optionally substituted aryloxycarbonyl, lower alkoxycarbonyl, nitro, hydroxy, carboxy, lower alkoxycarbonyl, cyano, oxo, carboxy lower alkenyl, SO₂-cyclic amino (preferably 5-6 membered ring), lower alkylsulfonylamino, optionally substituted amino (for example: lower alkyl, lower alkoxy, acyl (e.g., lower alkylcarbonyl, amino lower alkylcarbonyl, lower alkylamino lower alkylcarbonyl), heterocycle (preferably 5-6 membered ring)), optionally substituted amino lower alkyl, optionally substituted carbamoyl (for example: lower alkyl, CN, OH), optionally substituted carbamoyloxy, halo, lower alkyl halide, lower alkoxy halide, lower alkylthio halide, lower alkylcarbonyl halide, heterocyclo lower alkyl, heterocyclo lower alkoxy, cycloalkyl lower alkoxy, optionally substituted aralkyloxy, optionally substituted heteroaryl (preferably 5-6 membered ring), optionally substituted heteroaryl-lower alkyl, optionally substituted heteroaryl-lower alkyloxy, optionally substituted heterocycle, optionally substituted heterocycle lower alkyl, optionally substituted heterocycle lower alkyloxy, optionally substituted heterocyclecarbonyl lower alkenyl, optionally substituted heterocycleamino, optionally substituted aryl, and optionally substituted heterocyclecarbonyl lower alkenyl, SCO₂R, OC(═S)OR, OC(═O)SR, C(═S)OR, SC(═O)SR, SC(═S)SR, OC(═S)NH₂, SC(═O)NH₂, SC(═S)NH₂, OC(═S)NHR, SC(═O)NHR, SC(═S)NHR, OSO₂NHR, OSO₂NHPh, OC(═S)NR₂, SC(═O)NR₂, SC(═S)NR₂, C(═S)NH₂, C(═S)NHR, C(═S)NR₂ (R is lower alkyl), CONHCN, CONHOH, etc.

The optionally substituted amino as described above is for example amino, mono- or di-lower alkylamino, phenylamino, N-alkyl-n-phenylamino, mono- or di-lower alkoxy lower alkylamino, mono- or di-hydroxy lower alkylamino lower alkoxycarbonylamino, lower alkylcarbamoylamino, lower alkylcarbonylamino, NHC(═O)SR, NHC(═S)OR, NHC(═S)SR, NHC(═S)R, NH(CH₂)₂OH, N[(CH₂)₂OH]₂ (R is lower alkyl), optionally substituted heterocycleamino (substituent: lower alkyl), optionally substituted acetylamino (for example: optionally substituted heterocycle (substituent: e.g., lower alkyl), amino, alkylamino), etc. The substituent of the above optionally substituted aryl, aralkyl, heteroaryl, heterocycle includes, lower alkyl, lower alkoxy, lower alkoxy lower alkyl, heterocycle (preferably 5-6 membered ring), cyano, etc.

The substituent for “carbocycle or heterocycle which may have an unsaturated bond” in the definition for Ar1 and Ar2 is, more specifically, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, vinyl, allyl, propargyl, OH, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, t-butyloxy, vinyloxy, allyloxy, propargyloxy, benzyloxy, 2,3,4-picolyloxy, furfuryloxy, thiophenemethyloxy, imidazolylmethyloxy, pyrazolylmethyloxy, triazolylmethyloxy, thiazolylmethyloxy, oxazolylmethyloxy, isoxazolylmethyloxy, phenylethyloxy, 2,3,4-pyridylethyloxy, furylethyloxy, thiopheneethyloxy, imidazolylethyloxy, pyrazolylethyloxy, triazolylethyloxy, thiazolylethyloxy, oxazolylethyloxy, isoxazolylethyloxy, cyclopropylmethyloxy, cyclopentylmethyloxy, cyclohexylmethyloxy, tetrahydropyran-4-ylmethyloxy, [1,3]dioxolan-2-ylmethyloxy, OCO₂Me, NHCO₂Me, OCONHMe, NHCONHMe, NHCOMe, CONH₂, CONHMe, CONMe₂, OCONHPh, SCO₂Me, OC(═S)OMe, OC(═O)SMe, C(═S)OMe, SC(═O)SMe, SC(═S)SMe, NHC(═O)SMe, NHC(═S)OMe, NHC(═S)SMe, OC(═S)NH₂, SO₂NH₂, SO₂Me, SC(═O)NH₂, SC(═S)NH₂, OC(═S)NHMe, SC(═O)NHMe, SC(═S)NHMe, OSO₂NHMe, OSO₂NHPh, OC(═S)NMe₂, SC(═O)NMe₂, SC(═S)NMe₂, NHC(═S)Me, C(═S)NH₂, C(═S)NHMe, C(═S)NMe₂, NO₂, NH₂, NHMe, NMe₂, NHEt, NEt₂, NH(CH₂)₂OH), N[(CH₂)₂OH]₂, piperazinyl, 4-alkylpiperidino (e.g., 4-methylpiperidino), piperidinyl, morpholino, F, Cl, Br, CF₃, OCF₃, OCH₂CF₃, CN, oxo, etc. Ar1 or Ar2 may contain preferably 1 to 3 of these substituents.

For example, more preferred combinations of the substituents include 1) lower alkyl, aralkyloxy and nitro, 2) lower alkyl, aralkyloxy and amino, 3) lower alkyl, hydroxy and nitro, and 4) lower alkyl, hydroxy and amino, etc.

One preferred embodiment of Ar¹ is optionally substituted phenylene. Preferred substituent on phenylene include halo, hydroxy, hydroxy lower alkyl, optionally substituted lower alkoxy, optionally substituted amino (substituent: e.g., lower alkyl, heterocycle, heterocycle lower alkyl, lower alkoxy lower alkyl, hydroxy lower alkyl, lower alkylsulfonyl), optionally substituted amino lower alkyl, optionally substituted heterocycle, optionally substituted heterocycle lower alkyl, phenylene optionally substituted with heterocycle lower alkyl optionally substituted, optionally substituted carbamoyl (substituent: e.g., lower alkyl), optionally substituted carbamoyl lower alkenyl. Preferred heterocycle is a heterocycle optionally each substituted with lower alkyl such as morpholino, piperidino, piperidino), pyridyl etc.

One preferred embodiment of Ar¹ is optionally substituted 5 to 7-membered heterocycle. Preferred substituent on the heterocycle includes lower alkyl, oxo, halo, amino lower alkyl, mono- or di-lower alkylamino lower alkyl, lower alkoxy lower alkyl.

For Ar², aryl or heterocycle, optionally substituted with one or more substituent selected from the group consisting of halo, mono-, di- or tri-halogenated lower alkyl, mono-, di-, tri- or tetra-halogenated lower alkoxy, mono-, di-, tri- or tetra-halogenated lower alkylthio, mono- or di-lower alkylamino, cycloalkylmethyloxy, optionally substituted benzyloxy, lower alkoxycarbonylamino, nitro, heterocycle (e.g., morpholino, piperidino, piperidino, pyrrolidino optionally substituted independently with lower alkyl etc.), optionally substituted acetylamino, optionally substituted lower alkoxy, acyl (e.g., optionally substituted lower alkylcarbonyl), and optionally substituted lower alkyloxycarbonyl, is preferred.

The term “aralkyloxy” refers to a group wherein O atom is substituted the above “alkyl” substituted with the above “aryl” and, for example, benzyloxy, diphenylmethyloxy, triphenylmethyloxy, phenetyloxy, 1-naphythylmethyloxy, 2-naphythylmethyloxy, etc.

The term “lower alkoxy” refers to a group wherein O atom is substituted with the above “lower alkyl”, and for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, etc. Particularly, methoxy, ethoxy are preferred.

The term “aryloxy” refers to a group wherein O atom is substituted with the above “aryl”.

The term “optionally substituted amino” is an amino substituted or unsubstituted.

The term “optionally substituted carbamoyl” is a carbamoyl substituted or unsubstituted.

For substituents of “optionally substituted amino” and “optionally substituted carbamoyl” include, optionally substituted alkyl (e.g., methyl, ethyl, isopropyl, benzyl, carbamoylalkyl (e.g., carbamoylmethyl), mono- or di-alkylcarbamoylalkyl (e.g., dimethylcarbamoylethyl), hydroxyalkyl, heterocyclealkyl (e.g., morpholinoethyl, tetrahydropyranylethyl), alkoxycarbonylalkyl (e.g., ethoxycarbonylmethyl, ethoxycarbonylethyl), mono- or di-alkylaminoalkyl (e.g., dimethylamminioethyl) etc), alkoxyalkyl (e.g., methoxyethyl, ethoxymethyl, ethoxyethyl, i-propoxyethyl etc), acyl (e.g., formyl, optionally substituted alkylcarbonyl (e.g., acetyl, Propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, octanoyl, methoxyethylcarbonyl, 2,2,2-trifluoroethylcarbonyl, ethoxycarbonylmethylcarbonyl, alkoxyalkylcarbonyl (e.g., methoxyethylcarbonyl), alkylcarbamoylalkylcarbonyl (e.g., methylcarbamoylethylcarbonyl), alkoxycarbonylacetyl etc), optionally substituted arylcarbonyl (e.g., benzoyl, toluoyl etc)), optionally substituted aralkyl (e.g., benzyl, 4-F-benzyl etc), hydroxy, optionally substituted alkylsulfonyl (e.g., methanesulfonyl, ethanesulphonyl, isopropylsulphonyl, 2,2,2-trifluoroethanesulphonyl, benzylsulphonyl, methoxyethylsulphonyl etc), arylsulfonyl optionally substituted with alkyl or halo (e.g., benzenesulfonyl, toluenesulfonyl, 4-fluorobenzenesulfonyl), cycloalkyl (e.g., cyclopropyl etc), aryl optionally substituted with alkyl (e.g., 4-methylphenyl etc), alkylaminosulphonyl (e.g., methylaminosulphonyl, dimethylamminiosulphonyl etc), alkylaminocarbonyl (e.g., dimethylaminocarbonyl etc), alkoxycarbonyl (e.g., ethoxycarbonyl etc), cycloalkylcarbonyl (e.g., cyclopropylcarbonyl, cyclohexylcarbonyl etc), optionally substituted sulfamoyl (e.g., sulfamoyl, methylsulfamoyl, dimethylsulfamoyl etc), alkylcarbonylamino (e.g., methylcarbonylamino), heterocycle (e.g., morpholino, tetrahydropyranyl), optionally substituted amino (e.g., mono- or di-alkylamino (e.g., dimethylamminio), formylamino), etc. It may be mono- or di-substituted with the above substituent.

The amino group of “optionally substituted amino” and “optionally substituted carbamoyl” may be substituted with alkylene such as trimethylene, tetramethylene, pentamethylene, or the N atom of the amino group together to form a ring that may contain O, S atom.

For the amino group of “optionally substituted amino” and “optionally substituted carbamoyl”, the two substituents of the amino group taken together with a nitrogen atom to which they are attached form a nitrogen containing heterocycle that may contain S and/or O atom within the ring, preferably 5 to 7 membered and preferably saturated, and said ring may be substituted with oxo, lower alkyl or hydroxy etc. The ring may be substituted at S atom with oxo.

For example, 5 or 6-membered ring such as piperidino, piperidino, morpholino, pyrrolidino, thiazin-2-yl, 2-oxopiperidino, 2-oxopyrrolidino, 1,1-dioxido-1,2-thiazin-2-yl, 4-hydroxymorpholino are preferred.

Substituent of “optionally substituted aryl” and “optionally substituted heteroaryl” is that as described above for “optionally substituted amino group”.

Preferred embodiments of the group of the formula: —X¹—Ar¹—X²—Y—X³—Ar² for R^(A) are as follows:

(1) —CH₂— (Substituted) Ph-CONR—(Substituted Ph)

(2) —CH₂— (Substituted) Ph-NRCO—(Substituted Ph)

(3) —CH₂— (Substituted) Ph-CH₂—CONR—(Substituted Ph)

(4) —CH₂— (Substituted) Ph-CH₂—NRCO—(Substituted Ph)

(5) —CH₂— (Substituted) Ph-X—CONR—(Substituted Ph)

(6) —CH₂— (Substituted) Ph-X—NRCO—(Substituted Ph)

(7) —CH₂— (Substituted) Ph-Q-(Substituted Ph)

(8) —CH₂— (Substituted) Het-CONR—(Substituted Ph)

(9) —CH₂— (Substituted) Het-NRCO—(Substituted Ph)

(10) —CH₂— (Substituted) Ph-CONR—CH₂—(Substituted Ph)

(11) —CH₂— (Substituted) Ph-NRCO—CH₂—(Substituted Ph)

(12) —CH₂— (Substituted) Ph-CH₂—CONR—CH₂—(Substituted Ph)

(13) —CH₂-(Substituted) Ph-CH₂—NRCO—CH₂—(Substituted Ph)

(14) —CH₂— (Substituted) Ph-X—CONR—CH₂—(Substituted Ph)

(15) —CH₂— (Substituted) Ph-X—NRCO—CH₂—(Substituted Ph)

(16) —CH₂— (Substituted) Ph-Q-CH₂—(Substituted Ph)

(17) —CH₂— (Substituted) Het-CONR—CH₂—(Substituted Ph)

(18) —CH₂— (Substituted) Het-NRCO—CH₂—(Substituted Ph)

(19) —(CH₂)_(m)—(Substituted) Ph-CONR—(Substituted Ph)

(20) —(CH₂)_(m)—(Substituted) Ph-NRCO—(Substituted Ph)

(21) —(CH₂)_(m)—(Substituted) Ph-CH₂—CONR—(Substituted Ph)

(22) —(CH₂)_(m)—(Substituted) Ph-CH₂—NRCO—(Substituted Ph)

(23) —(CH₂)_(m)—(Substituted) Ph-X—CONR—(Substituted Ph)

(24) —(CH₂)_(m)—(Substituted) Ph-X—NRCO—(Substituted Ph)

(25) —(CH₂)_(m)—(Substituted) Ph-Q-(Substituted Ph)

(26) —(CH₂)_(m)—(Substituted) Het-CONR—(Substituted Ph)

(27) —(CH₂)_(m)—(Substituted) Het-NRCO—(Substituted Ph)

wherein, Ph=phenyl; R=hydrogen or lower alkyl; X═O or NH; Q is Q1 or Q2 as defined above; Het is heteroaryl or heterocycle (preferably 5 or 6-membered); M is 2 or 3; “Substitutied” means “optionally substituted”.

Chemically modified groups R^(B), R^(C), R^(D) include substituents as disclosed in Japanese Patent Publication 2001-163898. Examples of those substituents are specifically as bellows.

R^(B) can be selected from the groups as listed in (2-1)-(2-7):

(2-1) hydroxy:

(2-2) optionally substituted mono- or di-alkylamino (with the exception of the groups as described in (2-4)), wherein two alkyl moieties together form a ring, and wherein said substituent is amino, monoalkylamino, dialkylamino, trialkylammonium, hydroxy, guanidino, carboxy, alkyloxycarbonyl, carbamoyl optionally substituted with cyano, mono- or di-alkylcarbamoyl, mono- or di-arylcarbamoyl, aryl, alkylamido or arylamido, alkylurea or arylurea, —(C═O)N⁻—N⁺ (R^(X))₃, —N⁺ (R^(X))₂ (CH₂)_(m)COOR^(Y), —N⁺ (R^(X))₂(CH₂)_(m) N⁺ (R^(X))₃, —SO₂—OR^(y) or —P═O(OR^(y))₂ in which m is 1 to 3, R^(X) is C₁-C₃ alkyl, and R^(y) is hydrogen or C₁-C₃ alkyl, or combination of these substituents, and wherein alkyl in said substituent may further be substituted with alkyloxycarbonyl or aryloxycarbonyl and aryl ring in said substituent may further be substituted with alkyl optionally substituted with halo, nitro, amino, hydroxy, carboxy, alkyloxycarbonyl, or amino, hydroxyalkyl or thioalkyl optionally acylated, or combination thereof;

(2-3) cycloalkylamino optionally substituted with amino or hydroxy;

(2-4) di-substituted methylamino —NHCHR⁶R⁷, wherein R⁶ is selected from carboxy, optionally substituted alkyloxycarbonyl, carbamoyl, or optionally substituted monoalkylcarbamoyl, or optionally substituted cycloalkylcarbamoyl, wherein said substituent is amino, monoalkylamino, dialkylamino, trialkylammonium, carboxy, hydroxy, —(C═O)N⁻—N⁺ (R^(X))₃, aryl optionally substituted with —(CH₂)_(m)COOR^(X) in which m is 1 to 3 and R^(X) is C₁-C₃ alkyl, —N⁺ (R^(X))₂ (CH₂)_(m)COOR^(y), in which R^(y) is hydrogen or C₁-C₃ alkyl, or —N⁺ (R^(X))₂ (CH₂)_(m)N⁺ (R^(X))₃, or combination thereof, and wherein R⁷ is indole, thioindole or imidazolyl wherein the nitrogen atom is optionally substituted with C₁-C₃ alkyl;

(2-5) tripeptide R-A₁-A₂-A₃-: wherein A¹, A² and A³ are independently any amino acid unit, R is hydroxy, amino or optionally substituted mono- or di-alkylamino at the carboxy terminal of said tripeptide, and wherein said substituent is amino, monoalkylamino, dialkylamino, trialkylammonium, guanidino or aryl;

(2-6) hydrazino or hydroxamic acid which may be substituted with alkyl or arylalkyl optionally substituted further with alkyl; and

(2-7) alkoxy which may be substituted with arylcarbonyl optionally substituted with nitro, hydroxamic acid or alkyl;

with the proviso that any aryl ring present in the groups in (2-2)-(2-7) may contain a heteroatom, and any carbon-carbon single bond may be interrupted with a heteroatom or a heterogroup selected from —O(P═O)(OR^(F))O— (R^(F) is hydrogen, alkyloxycarbonyl or aryloxycarbonyl), and imino. R^(B) is preferably —OH, —NHR⁵, or —NHR⁵R⁵′ wherein R⁵ and R⁵′ is hydrogen, optionally substituted alkyl, —NH—R, —NH—COR, —NH—CONHR, —O—R (each R is independently hydrogen or optionally substituted alkyl), or amino sugar residue. Preferably, either of R⁵ and R⁵′ is hydrogen.

Preferred substituents for optionally substituted alkyl are hydrophilic substituents such as, for example, same or different 1 to 10, preferably 1 to 6, substituents selected from amino, mono- or di-lower alkylamino, trialkylamine, amino lower alkylamino, hydroxy lower alkylamino, hydroxy, carboxy, lower alkoxycarbonyl, SO₃H, PO₃H₂, optionally substituted carbamoyl, quaternary ammonium group (e.g., trialkylamino (e.g., —N⁺ (CH₃)₃)), optionally substituted heterocyclic group (heterocycle or heteroaryl), optionally substituted heterocyclic ring thio, guanidino, NHSO₂NH₂, hydroxy lower alkoxy. A nitrogen atom in the heterocyclic ring may be quaternized to form a salt. Substituents for the optionally substituted heterocyclic include hydroxy, amino, carboxy, amino lower alkyl, quaternary ammonium lower alkyl. The lower alkyl group on the quaternary ammonium group may further be substituted with substituted alkyl (substituent: carboxy, hydroxy, quaternary ammonium group).

R^(C) is selected from the group consisting of the following (3-1)-(3-4):

(3-1) hydrogen;

(3-2) aminomethyl optionally substituted with alkyl, cycloalkyl or alkylene, wherein said alkyl, cycloalkyl and alkylene may by substituted with amino optionally substituted with alkyloxycarbonyl or aryloxycarbonyl, monoalkylamino, dialkylamino, trialkylammonium, aryl optionally substituted with cycloalkyl, hydroxy, guanidino, —O— (P═O)(OH)₂, carboxy, —N⁺ (R^(X))₂ (CH₂)_(m)N⁺ (R^(X))₃, or —(C═O)—N⁻—N⁺ (R^(X))₃, in which m is 1 to 3, R^(X) is C₁-C₃ alkyl, or combination thereof, and wherein alkyl of said monoalkylamino or dialkylamino is further optionally substituted with amino;

(3-3) alkynyl that may have a substituent wherein said substituent is amino optionally substituted with alkyloxycarbonyl or aryloxycarbonyl, or aryl;

(3-4) halo;

with the proviso that any aryl ring present in the groups in (3-2) and (3-3) may contain a heteroatom, and any carbon-carbon single bond may be interrupted with a heteroatom or a heterogroup selected from —O(P═O)(OR^(F))O— (R^(F) is hydrogen, alkyloxycarbonyl or aryloxycarbonyl), amido or imino.

R^(C) is preferably hydrogen or optionally substituted alkyl. Substituent for such optionally substituted alkyl is preferably —NHR⁵ described above or those described above for optionally substituted alkyl in R⁵.

Preferred combination of R³ and R^(C) includes instance such as R^(B) is hydrogen, —NHR⁵ (R⁵ is mono- or di-lower alkylamino lower alkyl, tri-lower alkylammonium lower alkyl, or amino sugar residue), —NR⁵R⁵′ (R⁵ and R⁵′ is together hydroxy lower alkyl), or —NHCH₂CON—N⁺ (Me)₃; and

R^(C) is hydrogen, mono- or di-substituted amino lower alkyl (Example for substituent: lower alkyl, mono- or di-lower alkylamino lower alkyl, tri-lower alkylammonium lower alkyl, hydroxy lower alkyl, hydroxy lower alkoxy lower alkyl, —CH₂CON—N⁺ (Me)₃, lower alkyl substituted with 1 to 6 hydroxy, and carboxy, hydroxy, oxo, optionally substituted carbamoyl, guanidido, sulfonate group, phosphate group, lower alkyl substituted with NHSO₂NH₂ and/or amino, optionally substituted heterocycle lower alkyl (substituent: amino lower alkyl), optionally substituted quaternary ammonium lower alkyl (substituent: carboxy, hydroxy, quaternary ammonium group)). Specific combinations are provided in the following Tables 1-6 to 1-8. Also, other preferred embodiments are presented in the following Tables 47 to 53, 99 to 108.

R^(D) is selected from the group consisting of the following (4-1)-(4-6):

(4-1) hydrogen;

(4-2) alkyl that may have a substituent, wherein said substituent is alkyloxycarbonyl, amino, optionally alkylated aryl, arylcarbonyl, carbamoyl, mono- or di-alkylcarbamoyl or mono- or di-arylalkylcarbamoyl, or combination thereof, and wherein alkyl or aryl in said substituent further may be substituted with amino or hydroxy optionally substituted with alkyloxycarbonyl or aryloxycarbonyl;

(4-3) alkyloxycarbonyl that may be substituted with optionally alkylated aryl;

(4-4) arylamido or arylthioamido;

(4-5) amino or amidino optionally alkylated; and

(4-6) nitroso; with the proviso that any aryl ring present in the groups in (4-2) to (4-5) may contain a heteroatom, and any carbon-carbon single bond may be interrupted with a heteroatom. R^(D) is preferably hydrogen or optionally substituted alkyl. Also, the N-terminal moiety may be converted to —NH₂ by removing the leucine residue, and further optionally acylated, according to a procedure as described in literatures such as Expert Opin. Ther. Patents (2004) 14, 141-173 (e.g., Table 110).

Preferred compounds of the invention are categorized as follows:

1) A compound or pharmaceutically acceptable salt or solvate thereof wherein R^(A) is represented by the formula: — X¹—Ar¹—X²—Y—X³—Ar² in which each variable is as defined above;

2) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein Ar¹ and Ar² are optionally substituted aryl or optionally substituted heteroaryl or optionally substituted cycloalkyl;

3) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein Ar¹ and Ar² are optionally substituted benzene ring, and Y is —NHCO— or —CONH—;

4) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein X¹ is lower alkylene;

5) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein X² is a single bond, lower alkylene or a heteroatomic group as described above;

6) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein X³ is a single bond, lower alkylene or a heteroatomic group as described above;

7) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein R^(A) is represented by the formula:— X¹—Ar¹—X²—Y—X³—Ar² in which X¹ is lower alkylene; X² is a single bond, lower alkylene or a heteroatomic group as described above; X³ is a single bond, lower alkylene or a heteroatomic group as described above; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted benzene ring; and Ar² is optionally substituted benzene ring, optionally substituted heterocycle or optionally substituted cycloalkyl;

8) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein R^(A) is represented by the formula: —X¹—Ar¹—X²-Q—Ar² or —X¹—Ar¹-Q—X³—Ar² in which X¹ is lower alkylene; X² and X³ are a single bond, lower alkylene or a heteroatomic group as described above; Ar¹ is optionally substituted benzene ring; and Ar² is optionally substituted benzene ring, optionally substituted heterocycle or optionally substituted cycloalkyl;

9) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein R^(A) is a benzene ring or a heterocycle optionally substituted with one or more substituent selected from the group consisting of lower alkyl, nitro, aralkyloxy, optionally substituted amino, hydroxy, halo, oxo, lower alkoxy, aryloxy, carbamoyl, optionally substituted carbamoyloxy, and heterocycle group; another preferred embodiment of Ar² is aryl optionally substituted with one or more substituent selected from the group consisting of halo, mono-, di- or tri-halogenated lower alkyl, mono-, di- or tri-halogenated lower alkoxy, mono-, di- or tri-halogenated lower alkylthio, mono- or di-lower alkylamino, cycloalkylmethyloxy, benzyloxy, lower alkoxycarbonylamino, and nitro; and

10) A compound, a pharmaceutically acceptable salt, or solvate thereof wherein amino sugar moiety is L-vancosaminyl, 3-desmethyl-vancosaminyl, 3-epi-vancosaminyl, 4-epi-vancosaminyl, 4-keto-vancosaminyl, acosaminyl, actinosaminyl, daunosaminyl, 3-epi-daunosaminyl, ristosaminyl, N-methyl-D-glucaminyl, N-Acetyl-D-glucosamyl, or N-acyl-D-glucosamyl, more preferably L-vancosaminyl.

The compound may be constituted with any combination of two or more of the above categories 1) to 10).

11) More preferred compound of the invention is that wherein R^(A) is a group represented by the formula: —X¹—Ar¹—X²—Y—X³—Ar² in which X¹ is lower alkylene; X² is a single bond; X³ is a single bond; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted benzene ring; and Ar² is optionally substituted benzene ring, optionally substituted heterocycle or optionally substituted cycloalkyl, preferably optionally substituted benzene ring. Substituent for Ar¹ includes optionally substituted amino and/or substituent for Ar² is preferably one or more selected from the group consisting of halo, mono-, di- or tri-halogenated lower alkyl, mono-, di- or tri-halogenated lower alkoxy, mono-, di- or tri-halogenated lower alkylthio, mono- or di-lower alkylamino, cycloalkylmethyloxy, benzyloxy, lower alkoxycarbonylamino, and nitro; R^(B) is —NR⁵R⁵′; R^(C) is a group other than hydrogen (preferably optionally substituted alkyl); and/or R^(D) is a group other than hydrogen (e.g., optionally substituted alkyl).

Preferred chemical modifications for R^(B) and R^(C) are as described above.

Another preferred embodiment of the compound is as follows.

12) Ar¹ is optionally substituted heteroaryl;

13) X¹ is lower alkylene; X² is a single bond, lower alkylene or a heteroatomic group as described above; X³ is a single bond, lower alkylene or heteroatomic group; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted heteroaryl; and Ar2 is optionally substituted phenyl, optionally substituted heterocycle or optionally substituted cycloalkyl;

14) R^(B) is —OH; R^(C) is hydrogen; and R^(D) is hydrogen;

15) R^(B) is —NR⁵R⁵, wherein R⁵ and R⁵′ are independently hydrogen, optionally substituted alkyl, or amino sugar residue; R^(C) is hydrogen; and R^(D) is hydrogen;

16) R^(B) is —NR⁵R⁵′ wherein R⁵ is hydrogen; R⁵′ is alkyl or, amino sugar residue substituted with a hydrophilic substituent; R^(C) is hydrogen; and R^(D) is hydrogen;

17) R^(B) is —OH; R^(C) is optionally substituted alkyl in which alkyl moiety may be interrupted with a heteroatomic group; and R^(D) is hydrogen;

18) R^(B) is —OH; R^(C) is alkyl substituted with a hydrophilic substituent in which alkyl moiety may be interrupted with a heteroatomic group; and R^(D) is hydrogen;

19) X¹ is lower alkylene; X² is a single bond, lower alkylene or a heteroatomic group; X³ is a single bond, lower alkylene or a heteroatomic group; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted phenyl or optionally substituted heteroaryl; Ar² is optionally substituted phenyl, optionally substituted heterocycle or optionally substituted cycloalkyl; and the compound meets at least one of the requirements 1)-3) for R^(B), R^(C) and R^(D):

-   -   1) R^(B) is —NR⁵R⁵′ wherein R⁵ and R⁵′ are independently         hydrogen, optionally substituted alkyl, or amino sugar residue;     -   2) R^(C) is optionally substituted alkyl in which alkyl moiety         may be interrupted with a heteroatomic group;     -   3) R^(D) is lower alkyl;

(20) X¹ is lower alkylene, preferably C₁-C₃ alkylene; X² is a single bond, lower alkylene or a heteroatomic group as described above (e.g., NH), preferably a single bond; X³ is a single bond, lower alkylene or heteroatomic group (e.g., NH), preferably a single bond; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted heteroaryl or optionally substituted heterocycle (preferably 5-6 membered ring); and Ar² is optionally substituted phenyl, optionally substituted heterocycle (preferably 5-6 membered ring) or optionally substituted cycloalkyl (preferably 3-7 membered ring). One of such embodiment includes compounds that further meet at least one of the requirements 1)-4) for R^(B), R^(C) and R^(D):

-   -   1) R^(B) is —OH, —NR⁵R⁵′ wherein R⁵ and R¹⁵¹ are independently         hydrogen, optionally substituted alkyl, —NH—R, —NH—COR,         —NH—CONHR, —O—R (each R is independently hydrogen or optionally         substituted alkyl) or amino sugar residue, or —OR⁶ (R⁶ is         optionally substituted alkyl in which alkyl moiety may be         interrupted with a heteroatomic group such as, preferably one to         two NH, O etc.);     -   2) R^(C) is optionally substituted alkyl in which alkyl moiety         may be interrupted with a heteroatomic group;     -   3) R^(D) is lower alkyl;     -   4) leucine residue has been removed at the N-terminal

More specifically, the compounds of the invention are listed bellow. TABLE 1 R^(A) R^(B) R^(C) R^(D)

OH or NH—R CH₂—NH—R H

OH or NH—R CH₂—NH—R H R^(B) R^(C) R^(D) —NH(CH₂)₂NMe₂ H H —NH(CH₂)₂N⁺Me₃ H H —NH(CH₂)₃NMe₂ H H —NH(CH₂)₃N⁺Me₃ H H —NH(CH₂)₂NH(CH₂)₂NH₂ H H —NH(CH₂)₂NH(CH₂)₂OH H H —N[(CH₂)₂OH)]₂ H H —NHCH₂CO₂H H H —NH(CH₂)₂CO₂H H H —NH(CH₂)₂SO₃H H H —NH(CH₂)₂PO₃H₂ H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H H —CH₂NHMe H H —CH₂NH(CH₂)₂NH₂ H H —CH₂NH(CH₂)₂NMe₂ H H —CH₂NH(CH₂)₂N⁺Me₃ H H —CH₂N[(CH₂)₂OH]₂ H —CH₂NHCH₂CO₂H H H —CH₂NH(CH₂)₂CO₂H H H —CH₂NH(CH₂)₂SO₃H H H —CH₂NHCH₂PO₃H₂ H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H H

H —NH(CH₂)₃NMe₂ —CH₂NH(CH₂)₂N⁺Me₃ H —NH(CH₂)₃NMe₂ —CH₂N[(CH₂)₂OH]₂ H —NH(CH₂)₃NMe₂

H —NH(CH₂)₃NMe₂

H —NH(CH₂)₃NMe₂

H —NH(CH₂)₂N⁺Me₃ —CH₂NH(CH₂)₂N⁺Me₃ H —NH(CH₂)₂N⁺Me₃ —CH₂N[(CH₂)₂OH]₂ H —NH(CH₂)₂N⁺Me₃

H —NH(CH₂)₂N⁺Me₃

H —NH(CH₂)₂N⁺Me₃

H —N[(CH₂)₂OH]₂ —CH₂NH(CH₂)₂N⁺Me₃ H —N[(CH₂)₂OH)]₂ —CH₂N[(CH₂)₂OH]₂ H —N[(CH₂)₂OH]₂

H —N[(CH₂)₂OH]₂

H —N[(CH₂)₂OH]₂

H —NH(CH₂)₂CO₂H —CH₂NH(CH₂)₂N⁺Me₃ H —NH(CH₂)₂CO₂H —CH₂N[(CH₂)₂OH]₂ H —NH(CH₂)₂CO₂H

H —NH(CH₂)₂CO₂H

H —NH(CH₂)₂CO₂H

H

—CH₂NH(CH₂)₂N⁺Me₃ H

—CH₂N[(CH₂)₂OH]₂ H

H

H

H

—CH₂NH(CH₂)₂N⁺Me₃ H

—CH₂N[(CH₂)₂OH]₂ H

H

H

H

TABLE 2 R^(A) R^(B) R^(C) R^(D)

OH or NH—R CH₂—NH—R H or Me R^(A) Ar2 R11 R12 R13 R14 R15 X3 Y X2 Ar1 X1 NO2 OH Me H H bond CONH bond

CH2 NO2 OMe Me H H bond CONH bond

CH2 NO2 OiPr Me H H bond CONH bond

CH2 NO2 OnBu Me H H bond CONH bond

CH2 NO2 OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NO2 O-Picolyl Me H H bond CONH bond

CH2 NO2 O-Furfuryl Me H H bond CONH bond

CH2 NO2 O-Thiophene methyl Me H H bond CONH bond

CH2 NO2 O-Cyclohexyl methyl Me H H bond CONH bond

CH2 NO2 O-Tetrahydro pyran-4-yl Me H H bond CONH bond

CH2 NO2 O-[1,3]dioxo- lan-2- ylmethyl Me H H bond CONH bond

CH2 NH2 OH Me H H bond CONH bond

CH2 NH2 OMe Me H H bond CONH bond

CH2 NH2 OiPr Me H H bond CONH bond

CH2 NH2 OnBu Me H H bond CONH bond

CH2 NH2 OBn H H H bond CONH bond

CH2 NH2 OBn Me H H bond CONH bond

CH2 NMe2 OH Me H H bond CONH bond

CH2 NMe2 OMe Me H H bond CONH bond

CH2 NMe2 OiPr Me H H bond CONH bond

CH2 NMe2 OnBu Me H H bond CONH bond

CH2 NMe2 OBn H H H bond CONH bond

CH2 NMe2 OBn Me H H bond CONH bond

CH2 NH(CH2)2OH OH H H H bond CONH bond

CH2 NH(CH2)2OH OMe H H H bond CONH bond

CH2 NH(CH2)2OH OiPr H H H bond CONH bond

CH2 NH(CH2)2OH OnBu H H H bond CONH bond

CH2 NH(CH2)2OH OBn H H H bond CONH bond

CH2 NH(CH2)2OH O-Picolyl H H H bond CONH bond

CH2 Pyperizin- N-yl OMe H H H bond CONH bond

CH2 Pyperazin- N-yl OMe H H H bond CONH bond

CH2 NHAc OH H H H bond CONH bond

CH2 NHAc OMe H H H bond CONH bond

CH2 NHAc OiPr H H H bond CONH bond

CH2 NHAc OnBu H H H bond CONH bond

CH2 NHAc OBn H H H bond CONH bond

CH2 NHAc O-Picolyl H H H bond CONH bond

CH2 NHCO2Me OBn H H H bond CONH bond

CH2 NHCONHMe OBn H H H bond CONH bond

CH2 NC(═S)NH2 OBn H H H bond CONH bond

CH2 OCONH2 OBn H H H bond CONH bond

CH2 CONHMe OBn H H H bond CONH bond

CH2 CN OH H H H bond CONH bond

CH2 CN OMe H H H bond CONH bond

CH2 CN OiPr H H H bond CONH bond

CH2 CN OnBu H H H bond CONH bond

CH2 CN OBn H H H bond CONH bond

CH2 CN O-Picolyl H H H bond CONH bond

CH2 OBn NO2 H H H bond CONH bond

CH2 OMe NO2 H H H bond CONH bond

CH2 OBn NHMe H H H bond CONH bond

CH2 OBn NHAc H H H bond CONH bond

CH2 OBn H NO2 H H bond CONH bond

CH2 OBn H H NO2 H bond CONH bond

CH2 OBn H H H NO2 bond CONH bond

CH2 NO2 H OBn H H bond CONH bond

CH2 NO2 H H OBn H bond CONH bond

CH2 NO2 H H H OBn bond CONH bond

CH2 NO2 H OMe H H bond CONH bond

CH2 NO2 H H OMe H bond CONH bond

CH2 NO2 H H H OMe bond CONH bond

CH2 NO2 Me OBn H H bond CONH bond

CH2 NHAc H OBn H H bond CONH bond

CH2 NHAc H H OBn H bond CONH bond

CH2 NHAc H H H OBn bond CONH bond

CH2 NHAc H OMe H H bond CONH bond

CH2 NHAc H H OMe H bond CONH bond

CH2 NHAc H H H OMe bond CONH bond

CH2 F OH Me H H bond CONH bond

CH2 F OMe Me H H bond CONH bond

CH2 F OiPr Me H H bond CONH bond

CH2 F OnBu Me H H bond CONH bond

CH2 F OBn H H H bond CONH bond

CH2 F OBn Me H H bond CONH bond

CH2 F O-Picolyl Me H H bond CONH bond

CH2 Cl OH Me H H bond CONH bond

CH2 Cl OMe Me H H bond CONH bond

CH2 Cl OiPr Me H H bond CONH bond

CH2 Cl OnBu Me H H bond CONH bond

CH2 Cl OBn H H H bond CONH bond

CH2 Cl OBn Me H H bond CONH bond

CH2 Cl O-Picolyl Me H H bond CONH bond

CH2 Br OBn Me H H bond CONH bond

CH2 OCF3 OBn Me H H bond CONH bond

CH2 NO2 F H H H bond CONH bond

CH2 NO2 Cl H H H bond CONH bond

CH2 NO2 Br H H H bond CONH bond

CH2 NO2 OCF3 H H H bond CONH bond

CH2 NHAc F Me H H bond CONH bond

CH2 NHAc Cl Me H H bond CONH bond

CH2 NHAc Br Me H H bond CONH bond

CH2 NHAc OCF3 Me H H bond CONH bond

CH2 NO2 OCONHPh H H H bond CONH bond

CH2 NO2 OCONHMe H H H bond CONH bond

CH2 CN OCONHPh H H H bond CONH bond

CH2 CN OCONHMe H H H bond CONH bond

CH2 H SO2NHPh H H H bond CONH bond

CH2 NO2 SO2NHMe H H H bond CONH bond

CH2 NO2 OH H H H bond CONMe bond

CH2 NO2 OMe H H H bond CONMe bond

CH2 NO2 OiPr H H H bond CONMe bond

CH2 NO2 OnBu H H H bond CONMe bond

CH2 NO2 OBn H H H bond CONMe bond

CH2 NO2 OBn Me H H bond CONMe bond

CH2 NO2 O-Picolyl H H H bond CONMe bond

CH2 NO2 OBn H H H CH2 CONH bond

CH2 NO2 OMe H H H CH2 CONH bond

CH2 NHMe OMe H H H CH2 CONH bond

CH2 NO2 OBn H H H O CONH bond

CH2 NO2 OMe H H H O CONH bond

CH2 NHMe OMe H H H O CONH bond

CH2 NO2 OBn H H H NH CONH bond

CH2 NO2 OMe H H H NH CONH bond

CH2 NHMe OMe H H H NH CONH bond

CH2 NO2 OBn H H H bond CONH CH2

CH2 NO2 OMe H H H bond CONH CH2

CH2 NHMe OMe H H H bond CONH CH2

CH2 NO2 OBn H H H bond NHCO O

CH2 NO2 OMe H H H bond NHCO O

CH2 NHMe OMe H H H bond NHCO O

CH2 NO2 OBn H H H bond NHCO NH

CH2 NO2 OMe H H H bond NHCO NH

CH2 NHMe OMe H H H bond NHCO NH

CH2 NHMe OBn H H H bond NMeCO O

CH2 NHMe OBn H H H bond NMeCO NH

CH2 NHMe OBn H H H

CH2 NHMe OBn H H H

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NHMe OBn H H H bond CONH bond

CH2 NO2 OBn Me H H bond CONH bond

(CH2)2 NO2 OBn Me H H bond CONH bond

(CH2)2 NO2 OBn Me H H bond CONH bond

(CH2)2 NHMe OBn H H H bond CONH bond

(CH2)2 NHMe OBn H H H bond CONH bond

(CH2)2 NHMe OBn H H H bond CONH bond

(CH2)2 NO2 OBn Me H H bond CONH bond

(CH2)3 NHMe OBn H H H bond CONH bond

(CH2)3

bond CONH bond

CH2

bond CONH bond

CH2

bond CONH bond

CH2

bond CONH bond

CH2

bond CONH bond

CH2

bond CONH bond

CH2

bond CONH bond

CH2

bond CONH bond

CH2

bond CONH bond

CH2

bond CONH bond

CH2

In the above tables, Me: methyl, Et: ethyl, Pr: n-propyl, iPr: isopropyl, iBu: isobutyl, tBu: t-butyl, bond: single bond

Table 1 provides an illustrative expansion of R^(B), R^(C) and R^(D) with respect to each of two R^(A), and Table 2 provides an illustrative expansion of R^(A) with respect to two of R^(B), R^(C) and R^(D). The compound of the invention includes any combination of the groups listed in Table 1 and Table 2.

The present invention encompasses the compounds as described above, a pharmaceutically acceptable salt and solvate thereof. Any theoretically available tautomer and geometric isomer of such compound are also within the scope of the present invention.

The term “pharmaceutically acceptable” means harmless with respect to the prevention and the treatment. Pharmaceutically acceptable salts of a compound of the present invention include, as basic salts, for example, alkali metal salts such as sodium or potassium salts; alkaline-earth metal salts such as calcium or magnesium salts; ammonium salts; aliphatic amine salts such as trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine or procaine salts, meglumine salt, diethanolamine salt or ethylenediamine salt; aralkyl amine salts such as N,N-dibenzylethylenediamine salts, benethamine salt; heterocyclic aromatic amine salts such as pyridine salts, picoline salts, quinoline salts or isoquinoline salts; quaternary ammonium salts such as tetramethylammonium salts, tetraethylammonium salts, benzyltrimethylammonium salts, benzyltriethylammonium salts, benzyltributylammonium salts, methyltrioctylammonium salts or tetrabutylammonium salts; and basic amino acid salts such as arginine salts or lysine salts. Acid salts include, for example, mineral acid salts such as hydrochloride, sulfates salts, nitrate salts, phosphates salts, carbonates salts, hydrogencarbonates or perchlorate; organic acid salts such as acetates, propionates, lactates, maleates, fumarates, tararic acid salts, malates, citrates salts, or ascorbates; sulfonates such as methanesulfonates, isethionates, benzenesulfonates, or p-toluenesulfonates; and acidic amino acid salts such as aspartates or glutamates.

Furthermore, various solvates of a compound of the present invention, for example, monosolvate, disolvate, monohydrate or dihydrate are also within the scope of the present invention

(2) General Procedure

Below is described a representative procedure for the production of a compound of the invention. The preparation of the compound is not intend to limit to such procedure, and of cause, can be conducted by another procedure.

The compound of the invention may be synthesized using vancomycin or its known derivative as a starting material, by chemical modification of the amino moiety (R^(A)) at the amino sugar, or the C terminal (R^(B)), the resorcinol moiety (R^(C)), or the methylamino moiety at the N terminal (R^(D)). Such chemical modification can be conducted according to the procedure, for example, as disclosed in Japanese Patent Publication No. 7-258289, WO00/39156, Japanese Patent Publication No. 2001-163898. Specifically, it may be conducted in the following manner.

1) Modification of R^(A) Moiety

Typically, vancomycin as a starting material may be reacted, optionally in the presence of a base, with a different aldehyde corresponding to R^(A) moiety of the formula —X¹—Ar¹—X²—Y—X³—Ar² to form an intermediate Schiff base, followed by reduction to N-alkylate to afford a desired secondary amine.

The Schiff base formation is conducted specifically in a polar solvent such as dimethylformamide or methanol or mixture thereof, optionally under inert atmosphere such as nitrogen or argon gas and optionally in the presence of a base, at a temperature between about 25° C. and about 100° C. Preferably, the reaction is conducted at room temperature to 100° C., preferably about 60° C. to about 80° C., for about 30 minute to 2 hours. The base used in the reaction is, for example, alkylamine (e.g., diisopropylethylamine, etc). The intermediate Schiff base, preferably without purification, may be reduced with a hydrogenated metal complex or subjected to a catalytic reduction. A metal borohydride, such as sodium borohydride or sodium cyanoborohydride, may be used as a hydrogenated metal complex. The catalytic reduction may be conducted using hydrogen in the presence of homogeneous or heterogeneous catalysis such as Crabtree catalyst, Wilkinson catalyst, palladium on carbon, platinum on carbon or rhodium on carbon. The reduction reaction is conducted at about 25° C. to about 100° C. for about 1 to 24 hours. Preferably, the reaction is conducted in the above solvent, using an excessive amount (e.g., 3-5 equiv) of sodium cyanoborohydride at about 60° C. to about 80° C.

2) Modification of R^(B) Moiety

Typically, vancomycin as a starting material may be subjected to amidation of the carboxylic acid moiety at the C terminal to provide a different amido derivative wherein R^(B)=—NR⁵R⁵′, according to a conventional procedure.

3) Modification of R^(C) Moiety

Typically, vancomycin as a starting material may be subjected to alkylation of the resorcinol moiety, according to a conventional procedure.

4) Modification of R^(D) Moiety

Typically, vancomycin as a starting material may be subjected to N-alkylation of the methylamine moiety at the N-tarminal, according to a conventional procedure.

(3) Pharmaceutical Composition

The invention also provides a pharmaceutical formulation comprising a novel glycopeptide derivative of the invention. Thus, the glycopeptide compound in a form of pharmaceutically acceptable salt may be formulated preferably for oral or parenteral administration for therapeutic and prophylactic treatment of bacterial infection.

For oral administration, the compounds of the present invention can be used in any form of usual formulations, for example, solid formulations such as tablets, powders, granules, capsules; aqueous formulations; oleaginous suspensions; solutions such as syrup or elixir. For parenteral administration, the compounds of the present invention can be used as an aqueous or oleaginous suspension injection, or nose drops. In the preparation of such formulations, conventional excipients, binding agents, lubricants, aqueous solvents, oleaginous solvents, emulsifying agents, suspending agents, preservatives, stabilizers, and the like can be optionally used. Preferred is an oral agent or an intravenous injection as an antimicrobial agent.

A formulation according to the present invention may be manufactured by combining (for example, admixing) a therapeutically effective amount of a compound of the present invention with a pharmaceutically acceptable carrier or diluent. The formulation of the present invention may be manufactured with well-known and easily available ingredients in accordance with a known method.

In the case of manufacturing a pharmaceutical composition according to the present invention, an active ingredient is admixed or diluted with a carrier, or they are contained in a carrier in the form of capsule, sacheier, paper, or another container. In the case of functioning a carrier as a diluent, the carrier is a solid, semi-solid, or liquid material which functions as a medium. Accordingly, a formulation according to the present invention may be produced in the form of tablet, pill, powder medicine, intraoral medicine, elixir agent, suspending agent, emulsifier, dissolving agent, syrup agent, aerosol agent (solid in liquid medium), and ointment. Such a formulation may contain up to 10% of an active compound. It is preferred to formulate a compound of the present invention prior to administration.

Any suitable carrier well known to those skilled in the art may be used for the formulation. In such formulation, a carrier is in the form of solid, liquid, or a mixture of solid and liquid. For instance, a compound of the present invention is dissolved into 4% dextrose/0.5% sodium citrate aqueous solution for intravenous injection. Solid formulation includes powder, tablet, and capsule. Solid carrier consists of one or more of material(s) for serving also as fragrant, lubricant, dissolving agent, suspension, binder, tablet disintegrator, capsule. A tablet for oral administration contains a suitable excipient such as calcium carbonate, sodium carbonate, lactose, calcium phosphate and the like together with a disintegrator such as corn starch, alginic acid and the like and/or a binder such as gelatin, acacia and the like, and a lubricant such as magnesium stearate, stearic acid, talc and the like.

In a powder medicine, a carrier is a finely pulverized solid which is blended with finely pulverized active ingredients. In a tablet, active ingredients are admixed with a carrier having required binding power in a suitable ratio, and it is solidified in a desired shape and size. Powder medicine and tablet contain about 1 to about 99% by weight of the active ingredients being novel compounds according to the present invention. Example of suitable solid carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth gum, methyl cellulose, sodium carboxymethylcellulose, low-melting wax, and cocoa butter.

A liquid formulation includes suspending agent, emulsifier, syrup agent, and elixir agent. Active ingredients may be dissolved or suspended into a pharmaceutically acceptable carrier such as sterile water, a sterile organic solvent, a mixture thereof and the like. Active ingredients may be dissolved frequently into a suitable organic solvent such as propylene glycol aqueous solution. When finely pulverized active ingredients are dispersed into aqueous starch, sodium carboxylmethylcellulose solution, or suitable oil, the other compositions can be prepared.

Although an appropriate dosage of the compound of the present invention varies depending on the administration route, age, body weight, conditions of the patient, and kind of disease, in the case of oral administration, the daily dosage can be between approximately 0.1-7000 m g, preferably approximately 0.5-2000 m g, for an adult. The daily dosage can be administered in divisions. In the case of parenteral administration, the daily dosage for an adult can be between approximately 0.1-1000 m g, preferably approximately 0.5-500 mg.

EXAMPLES

The present invention is further explained by the following Examples, which are not intended to limit the scope of the present invention in any way.

MS data in the following Preparations and Examples are expressed as a calculated average molar weight (C=12.0107, H=1.0079, O=15.9994, N=14.0067, Cl=35.4527, P=30.9738, Na=22.9898).

Preparation 1 Preparation of carboxylic acid 3

Carboxylic acid 3 was prepared as follows.

To a solution of 3.943 g (20.0 mmol) of 4-methyl-3-hydroxy-2-nitrobenzoic acid 1 (Aldrich) in 40 mL of dry DMF was added 4.98 mL (42 mmol) of benzyl bromide and finely powdered K₂CO₃ 5.8 g (42 mmol). This mixture was stirred at 65° C. under argon for 40 h. The reaction was worked up by pouring the solution into water and EtOAc. The product was extracted with EtOAc (3×40 mL). The ethyl acetate layers were combined, washed with water and brine, and dried over MgSO₄. Filtration and evaporation in vacuo gave a viscous yellow oil 2. R_(f)=0.87 (EtOAc:EtOH=4:1). ¹H NMR (CDCl₃): 7.76 (d, J=8.00, 1H), 7.42 (m, 11H), 5.33 (s, 2H), 4.96 (s, 2H), 2.40 (s, 3H).

Hydrolysis of crude ester 2 was carried out with 5.6 g (100 mmol) KOH, 20 mL of THF, 20 mL of water, and 30 mL CH₃OH. The reaction was stirred until TLC analysis showed complete consumption of starting material (about 16 h). The reaction was acidified and extracted with chloroform (3×30 mL). The chloroform layers were combined and washed with water and dried over MgSO₄. Filtration and evaporation of the solvent in vacuo left a pale yellow powder. The product was recrystallized from EtOAc/hexane to give 4.984 g (86%) of white crystals. R_(f)=0.60 (EtOAc:EtOH=4:1). ¹H NMR (CDCl₃): 7.82 (d, 1H, J=8.04 Hz), 7.38-7.43 (m, 6H), 4.98 (s, 2H), 2.43 (s, 3H).

Example 1

Aldehyde 5 was prepared from the carboxylic acid 3, and the aldehyde was then reacted with vancomycin to afford the desired compound.

Compound 4

A mixture of 0.574 g (2 mmol) of the acid 3, 0.226 mL (2.6 mmol, 1.3 equiv) of oxalyl chloride, 20 mL of dichloromethane, and 2 drops of DMF was heated to reflux for 40 min. The dichloromethane and excess oxalyl chloride was distilled until a viscous, yellow oil was obtained. The residue was dissolved in THF and quickly transferred to a 100 mL round-bottom flask containing 0.246 g (2 mmol) 4-aminobenzyl alcohol (Wako), 0.348 mL (2.5 mmol) of triethylamine, and 10 mL THF all cooled to 0° C. in an ice bath. After addition of the acid chloride, the solution was stirred at 0° C. for 30 min. The reaction was worked up by pouring the solution into a flask containing EtOAc and aqueous NaHCO₃. The product was extracted with ethyl acetate (3×30 mL). The ethyl acetate extracts were combined and washed with water and brine and dried over MgSO₄. Filtration and evaporation of solvent in vacuo afforded the product as a pale yellow solid. The product was recrystallized from EtOAc/hexane to give 0.588 g (75%) of white crystals. ¹H NMR (CDCl₃): 7.74 (s, 1H,), 7.55 (d, 2H, J=7.60 Hz), 7.34 (d, 2H, J=7.60 Hz), 7.36-7.45 (m, 7H), 5.02 (s, 2H), 4.67 (s, 2H), 2.40 (s, 3H).

Compound 5

A mixture of 0.588 g of compound 4, 3 g of MnO₂ and 20 mL of dichloromethane was stirred at room temperature for 3 h until TLC analysis showed complete consumption of starting material. Evaporation of solvent in vacuo give 0.46 g (77%) of pale yellow solid. ¹H NMR (CDCl₃): 9.95 (s, 1H,), 7.89 (d, 2H, J=8.32 Hz), 7.76 (d, 2H, J=8.32 Hz), 7.39-7.45 (m, 7H), 5.03 (s, 2H), 2.43 (s, 3H).

Compound 6

0.114 mL (2 eq.) of diisopropylethylamine (DIEA) was added to a solution of 0.495 g (0.333 mmol, 1 eq.) vancomycin in DMF/MeOH (1:1, 20 mL) and the 0.13 g (0.333 mmol, 1 eq.) aldehyde 5. The solution was heated at 70° C. for 2 h and then allowed to cool to room temperature. After 0.0836 g (1.332 mmol, 4 eq.) NaBH₃CN was added, the reaction mixture was stirred at 70° C. for an additional 24 h, and allowed to cool to ambient temperature overnight. Then poured into 400 mL of Et₂O. The white precipitate was isolated by centrifugation. Purification of precipitate by reverse-phase column chromatography yielded 0.376 g (62%) of compound 6 as a white solid: R_(f)=0.45 (CH₃CN:H₂O:TFA=1:1:0.01), MS (MALDI-TOF, CHCA) calcd for C₈₈H₉₃Cl₂N¹¹NaO₂₈[M+Na]⁺ 1846.63, found 1846.15.

Example 2

Compound 10 was prepared as described in Example 1.

Compound 8

A mixture of 0.574 g (2 mmol) of the acid 3, 0.226 mL (2.6 mmol, 1.3 equiv) of oxalyl chloride, 20 mL of dichloromethane, and 2 drops of DMF was heated to reflux for 40 min. The dichloromethane and excess oxalyl chloride was distilled until a viscous, yellow oil was obtained. The residue was dissolved in THF and quickly transferred to a 100 mL round-bottom flask containing 0.246 g (2 mmol) 3-aminobenzyl alcohol (Wako), 0.348 mL (2.5 mmol) of triethylamine, and 10 mL THF all cooled to 0° C. in an ice bath. After addition of the acid chloride, the solution was stirred at 0. ° C. for 30 min. The reaction was worked up by pouring the solution into a flask containing EtOAc and aqueous NaHCO₃. The product was extracted with ethyl acetate (3×30 mL). The ethyl acetate extracts were combined and washed with water and brine and dried over MgSO₄. Filtration and evaporation of solvent in vacuo afforded the product as a pale yellow solid. The product was purified by column chromatography (EtOAc) yielded 0.678 g (86%) compound 8. R_(f)=0.62 (EtOAc), ¹H NMR (CDCl₃): 7.78 (s, 1H,), 7.63 (s, 1H), 7.36-7.45 (m, 9H), 7.19 (d, 1H, J=7.60 Hz), 5.03 (s, 2H), 4.72 (s, 2H), 2.42 (s, 3H).

Compound 9

A mixture of 0.678 g of compound 8, 3.07 g of MnO₂ and 20 mL of dichloromethane was stirred at room temperature for 2 h until TLC analysis showed complete consumption of starting material. Evaporation of solvent in vacuo give 0.554 g crude product, and purified by column chromatography (EtOAc) yielded 0.491 g (73%) compound 9. ¹H NMR (CDCl₃): 10.01 (s, 1H,), 7.92 (d, 1H, J=7.60 Hz), 7.85 (s, 1H), 7.71 (d, 1H, J=8.00 Hz), 7.54 (t, 1H, J=8.00 Hz), 7.37-7.45 (m, 7H), 5.03 (s, 2H), 2.42 (s, 3H).

Compound 10

0.114 mL (2 eq.) DIEA was added to a solution of 0.495 g (0.333 mmol, 1 eq.) vancomycin in DMF/MeOH (1:1, 20 mL) and the 0.13 g (0.333 mmol, 1 eq.) aldehyde 9. The solution was heated at 70° C. for 2 h and then allowed to cool to room temperature. After 0.0836 g (1.332 mmol, 4 eq.) NaBH₃CN was added, the reaction mixture was stirred at 70° C. for an additional 24 h, and allowed to cool to ambient temperature overnight. Then poured into 400 mL of Et₂O. The white precipitate was isolated by centrifugation. Purification of precipitate by reverse-phase column chromatography yielded 0.565 g (93%) of compound 10 as a white solid: R_(f)=0.51 (CH₃CN:H₂O:TFA=1:1:0.01), MS (MALDI-TOF, CHCA) calcd for C₈₈H₉₃Cl₂N₁₁NaO₂₈ [M+Na]⁺1846.63, found 1846.37.

Example 3

Compound 11

A solution of compound 10 obtained in Example 2 (51.8 m g, 0.028 mmol) in methanol (3 mL) was reduced with hydrogen in the presence of 10% Pd—C catalyst (50 mg) (about 3 h) to give the corresponding aminophenol 11. MS (MALDI-TOF, CHCA) calcd for C₈₁H₈₉Cl₂N₁₁NaO₂₆ [M+Na]⁺1726.53, found 1726.67.

Example 4

Compound 16 was prepared as described in Example 1.

Compound 13

A mixture of 2.87 g (10.0 mmol) of the acid 3 (as prepared in Preparation 1), 1.13 mL (1.3 equiv) of oxalyl chloride, 80 mL of dichloromethane, and 2 drops of DMF was heat to reflux for 40 min. The dichloromethane and excess oxalyl chloride was distilled until a viscous, yellow oil was obtained. The residue was dissolved in THF and quickly transferred to a 250 mL round-bottom flask containing 0.92 mL (12 mmol, 1.2 equiv) of 3-amino-1-propanol, 3.48 mL (25 mmol, 2.5 equiv) of triethylamine, and 80 mL of THF all cooled to 0° C. in an ice bath. After addition of the acid chloride, the solution was stirred at 0° C. for 30 min. The reaction was worked up by pouring the solution into a flask containing EtOAc and aqueous NaHCO₃. The product was extracted with ethyl acetate (3×40 mL). The ethyl acetate extracted were combined and washed with water and brine and dried over MgSO₄. Filtration and evaporation of solvent in vacuo afforded the product as a viscous pale yellow oil. This crude material was subjected to the next reaction without further purification. R_(f)=0.65 (EtOAC:EtOH=4:1),

¹H NMR 7.28-7.42 (m, 7H,), 4.98 (s, 2H), 3.73 (t, 2H, J=5.60 Hz), 3.55 (q, 2H, J=5.60 Hz), 2.36 (s, 3H), 1.77 (m, 2H).

Compound 14

To a stirred solution of thionyl chloride (2.04 mL, 28 mmol) in DMF (10 mL) at 0° C. under argon were added KI (24.5 g, 0.15 mol in 70 mL of DMF) and the alcohol 13 (10 mmol in 30 mL of DMF) through syringe. The reaction mixture was stirred at 50° C. for the 3 h and then quenched with water and extracted with ether (3×100 mL). The combined ether extracts were washed successively with aqueous sodium thiosulfate solution and water. The organic solution was dried over anhydrous MgSO₄. Filtration and evaporation of solvent in vacuo afforded the product as a pale yellow solid. The product was recrystallized from EtOAc/hexane to give 2.41 g (53.1%, two steps) of pale yellow crystals. ¹H NMR 7.36-7.43 (m, 6H,), 7.28 (d, 1H, J=8.40 Hz), 4.99 (s, 2H), 3.51 (q, 2H, J=6.40 Hz), 3.24 (t, 2H, J=6.40 Hz), 2.38 (s, 3H), 2.12 (m, 2H).

Compound 15

To a solution of 4-hydroxybenzaldehyde (0.336 g, 2.75 mmol) in 10 mL of acetone were added anhydrous potassium carbonate (0.345 g, 2.5 mmol) and compound 14 (1.135 g, 2.5 mmol). The reaction was heat to reflux for 20 h. The mixture was cooled to room temperature, and then poured into 200 mL of water. Filtration afforded the product as a white solid, and purified by column chromatography (5% MeOH/CHCl₃) yielded 0.504 g (45%) of compound 15. R_(f)=0.50 (CHCl₃:MeOH=95:5), ¹H NMR (CDCl₃): 9.89 (s, 1H,), 7.84 (d, 2H, J=8.40 Hz), 7.27-7.41 (m, 7H), 7.27 (s, 1H), 7.01 (d, 2H, J=8.40 Hz), 4.99 (s, 2H), 4.17 (t, 2H, J=6.00 Hz), 3.64 (t, 2H, J=6.00 Hz), 2.38 (s, 3H), 2.15 (m, 3H).

Compound 16

0.114 mL (2 eq.) DIEA was added to a solution of 0.495 g (0.333 mmol, 1 eq.) vancomycin in DMF/MeOH (1:1, 20 mL) and the 0.149 g (0.333 mmol, 1 eq.) aldehyde 15. The solution was heated at 70° C. for 2 h and then allowed to cool to room temperature. After 0.0836 g (1.332 mmol, 4 eq.) NaBH₃CN was added, the reaction mixture was stirred at 70° C. for an additional 24 h, and allowed to cool to ambient temperature overnight. Then poured into 400 mL of Et₂O. The white precipitate was isolated by centrifugation. Purification of precipitate by reverse-phase column chromatography yielded 0.396 g (63%) of compound 16 as a white solid: R_(f)=0.34 (CH₃CN:H₂O:TFA=1:1:0.01), MS (MALDI, CHCA) calcd for C₉₁H₉₉Cl₂N₁₁NaO₂₉ [M+Na]⁺1904.71, found 1905.04.

Example 5

Compound 24

Compound 10 (as prepared in Example 2, 364.2 m g, 0.2 mmol) was dissolved in 4 mL of dry dimethyl sulfoxide (DMSO). To this was added 4 mL of dry dimethylformamide (DMF) and 50.4 μL (0.4 mmol, 2 equiv) of 3-(dimethylamino)propylamine (Nacalai). The mixture was cooled to 0° C., and 113.6 mg (0.3 mmol, 1.5 equiv) of HBTU (TCI) and 40.5 mg (0.3 mmol, 1.5 equiv) of HOBT (Wako) in 0.5 mL of DMF was added, followed by 17 μL (1 mmol, 5.0 equiv) of diisopropylethylamine (DIEA). The reaction was then allowed to warm to room temperature and was stirred overnight (about 12 h). The reaction mixture was poured into 200 mL of CH₂Cl₂. The resulting precipitate was filtered, washed with CH₂Cl₂, and dried under vacuum. Purification of precipitate by reverse-phase HPLC(Develosil ODS-HG-5, D 20 mm×250 mm, CH₃CN:H₂O:TFA=1:2:0.1%, flow rate 2 mL/min, UV: 215 nm, t_(R)=18.63 min) yielded 45.5 mg (45%) of compound 24 as a pale solid: MS (MALDI-TOF, CHCA) calcd for C₉₃H₁₀₅Cl₂N₁₃NaO₂₇ [M+Na]⁺1930.80, found 1931.59.

Example 6

Compound 26

(Aminomethyl)phosphonic acid (Aldrich) (155.4 m g, 1.4 mmol) and DIEA (0.24 mL, 1.4 mmol) were combined in water (1.5 mL) and stirred until homogenous. Acetonitrile (5 mL) and formaldehyde (37% solution in water, 16.5 μL, 0.22 mmol) were then added, followed by compound 10 (364.2 m g, 0.2 mmol) and DIEA (0.24 mL, 1.4 mmol). The mixture was stirred at room temperature for 20 h, then the solution was neutralized with 20% aqueous TFA. The acetonitrile was removed under reduced pressure, and the resulting suspension was lyophilized. The recovered solid was purified by reverse-phase HPLC(Develosil ODS-HG-5, D 20 mm×250 mm, CH₃CN:H₂O:TFA=1:1:0.1%, flow rate 3 mL/min, UV: 215 nm, t_(R)=13.58 min) yielded 66.1 mg (17%) of compound 26: MS (MALDI-TOF, CHCA) calcd for C₉₀H₉₉Cl₂N₁₂NaO_(3l)p

[M+Na]⁺1969.68, found 1967.77.

Example 7 Compound 27

0.114 mL (2 equiv) of diisopropylethylamine (DIEA) was added to chloroorienticin B (0.495 g, 0.333 mmol, 1 equiv) and aldehyde 19 (0.0857 g, 0.333 mmol, 1 equiv) in 1:1 dimethylformamide (DMF)/methanol (MeOH) (20 mL). The solution was heated at 70° C. for 3 hours and then cooled to room temperature. 0.084 g of sodium cyano borohydride (NaBH₃CN) (1.332 mmol, 4 equiv) was added, and the reaction mixture was stirred at 70° C. for additional 24 hours, and allowed to cool to ambient temperature overnight. Then poured into 300 mL of diethylether (Et₂O). The precipitate was isolated by centrifugation. Purification of precipitate by HPLC (Develosil ODS-HG-5, (20 mm×250 mm, acetonitrile:water:trifluoroacetate (TFA)=1:2:0.1%, flow rate 3 mL/minute, UV:215 nm) yielded compound 27 (110.2 m g, 36%) as a pale yellow solid.

MS (MALDI-TOF, CHCA) Calculated for C₈₀H₈₆Cl₂N₁₀NaO₂₇ [M+Na]⁺1713.49, Found 1713.94.

Example 8 Compound 29

DIEA (0.114 mL, 2 equiv) was added to chloroorienticin B (0.495 g, 0.333 mmol, 1 equiv) and aldehyde 15 (0.149 g, 0.333 mmol, 1 equiv) in DMF/MeOH (1:1, 20 mL). The solution was heated at 70° C. for 2 h and then allowed to cool to room temperature. After 0.0836 g (1.332 mmol, 4 eq.) NaBH₃CN was added, the reaction mixture was stirred at 70° C. for an additional 24 h, and allowed to cool to ambient temperature overnight. Then poured into 400 mL of Et₂O. The white precipitate was isolated by centrifugation. Purification of precipitate by reverse-phase column chromatography yielded compound 29 (0.135 g, 22%) as a white solid.

MS (MALDI, CHCA) Calculated for C₉₁H₉₉Cl₂N₁₁NaO₂₉

[M+Na]⁺:1904.71, Found 1904.95.

Example 9 Compound 31

DIEA (0.114 mL, 2 equiv) was added to chloroorienticin B (0.495 g, 0.333 mmol, 1 equiv) and aldehyde 9 (0.13 g, 0.333 mmol, 1 equiv) in DMF/MeOH (1:1, 20 mL). The solution was heated at 70° C. for 2 h and then allowed to cool to room temperature. After 0.0836 g (1.332 mmol, 4 eq.) NaBH₃CN was added, the reaction mixture was stirred at 70° C. for additional 24 h, and allowed to cool to ambient temperature overnight. Then poured into 400 mL of Et₂O. The white precipitate was isolated by centrifugation. Purification of precipitate by reverse-phase column chromatography yielded compound 31 (0.205 g, 34%) as a white solid. MS (MALDI-TOF, CHCA) Calculated for C₈₈H₉₃Cl₂N₁₁NaO₂₈ [M+Na]⁺: 1846.63,

Found: 1846.64.

Example 10

Compound 37 was prepared from carboxylic acid 32 according to the following scheme.

Compound 33

5-nitro-3-trifluoromethyl benzoic acid 32 (34.2 g, 145.5 mmol) was added to oxalyl chloride (16.5 mL, 189 mmol) suspended in dichloromethane (500 mL). Obtained suspension is added with dimethylformamide (0.5 mL) and stirred at 45° C. for 1 hour. The reaction mixture was concentrated in vacuo and dissolved in THF (300 mL). The solution was added dropwise under nitrogen stream and ice cooling to 3-aminobenzyl alcohol (18.5 g, 150 mmol) and triethylamine (20.3 mL, 182 mmol).

The mixture was stirred at room temperature for 2 h, and the solution was concentrated in vacuo after filtration to isolate precipitated insoluble material. The obtained residue was added with water and diisopropylether, followed by filtrated to isolate the preciptated crystal to afford compound 33 as a pale yellow powder. Yield: 49.9 g (100%).

¹H-NMR (DMSO-d6) δ: 10.72 (1H, s), 9.06 (1H, s), 8.76 (1H, s), 8.69 (1H, s), 7.75 (1H, s), 7.70 (1H, d, J=8.1 Hz), 7.34 (1H, t, J=7.8 Hz), 7.11 (1H, d, J=7.6 Hz), 5.27 (1H, t, J=5.8 Hz), 4.54 (2H, d, J=6.1 Hz).

Compound 34

An aqueous solution of ammonium chloride (15M, 30 mL) was added to a suspension of compound 33 (49.9 g, 145.5 mmol) in ethanol (600 mL) and stirred at 90° C. to dissolve. The reaction mixture was added with iron (73 g, 1310 mmol) over 1 hour, stirred at 90° C. for 20 h. The reaction mixture was filtered though celite, and the solution was concentrated in vacuo. The residue was added with water, precipitated crystal was filtrated to isolate, and washed with diisopropylether to yield compound 34 as a pale yellow powder. Yield: 39.9 g (88%).

¹H-NMR (DMSO-d6) δ: 10.26 (1H, s), 7.75 (1H, s), 7.66 (1H, d, J=8.1 Hz), 7.38 (2H, d, J=5.6 Hz), 7.30 (1H, t, J=7.8 Hz), 7.06 (2H, d, J=9.1 Hz), 5.84 (2H, s), 5.22 (1H, t, J=5.6 Hz), 4.52 (2H, d, J=5.6 Hz).

Compound 35

Compound 34 (39.9 g, 128.6 mmol) in acetonitrile (280 mL) was added with 37% formalin (46.2 mL, 643 mmol) with stirring under ice-cooling, and then sodium cyanoborohydride (40.3 g, 643 mmol) was added. After acetic acid (40 mL) was dropped to the obtained mixture under ice-cooling, the mixture was stirred under ice-cooling for 30 min. 37% formalin (28 mL, 386 mmol) was added and stirred under ice-cooling for 60 min, and the obtained solution was concentrated in vacuo. The residue was added with 2N sodium hydroxide, pH was adjusted to 8-9 to cause precipitation. The precipitate was filtered to isolate, washed with water and diisopropylether to yield compound 35 as a pale yellow powder. Yield: 42.7 g (98%). ¹H-NMR (DMSO-d6) δ: 10.32 (1H, s), 7.73 (1H, s), 7.68 (1H, d, J=8.1 Hz), 7.50 (2H, d, J=12.6 Hz), 7.31 (1H, t, J=7.7 Hz), 7.08-7.06 (2H, m), 5.24 (1H, br s), 4.53 (2H, d, J=11.4 Hz), 3.05 (6H, s).

Compound 36

Oxalyl chloride (16.5 mL, 189 mmol) in dichloro methane (100 mL) was dropped to dimethylsulphoxide (26 mL, 267 mmol) in dichloromethane (100 mL) at −78° C. After the mixture was stirred at −78° C. for 15 minutes, a mixture of compound 35 (37.6 g, 111.2 mmol) in dichloromethane (300 mL) and dimethylsulphoxide (30 mL) was dropped at −78° C., and stirred at −30° C. for 1 hour. Triethylamine (47 mL, 334 mmol) in dichloro methane (50 mL) was added dropwise to the reaction mixture, and stirred at −20° C. for 30 minutes. The solution was concentrated in vacuo. The residue was added with water, filtered to isolate preciptated crystal, and washed with diisopropylether to yield compound 36 as pale yellow powder. Yield: 36 g (96%).

¹H-NMR (DMSO-d6) δ: 10.60 (1H, s), 10.03 (1H, s), 8.36 (1H, s), 8.10 (1H, d, J=10.6 Hz), 7.70 (1H, t, J=6.2 Hz), 7.62 (1H, t, J=9.1 Hz), 7.53 (2H, d, J=13.6 Hz), 7.10 (1H, s), 3.06 (6H, s).

Compound 37

A mixture of vancomycin hydrochloride (44.6 g, 30 mmol) and compound 36 (10.6 g, 31.5 mmol) in methanol (300 mL) and dimethylformamide (300 mL) was added with diisopropylethylamine (10.5 mL, 60 mmol) and stirred at 70° C. for 2 h. The reaction mixture was added with sodium cyanoborohydride (7.5 g, 120 mmol) and stirred at 70° C. for 12 h. The reaction mixture was poured into ether (1500 mL), and the precipitate was filtered to isolate and purified by reverse-phase column chromatography, and lyophilized to yield compound 37 as white powder.

Yield: 17.1 g (28%).

Elemental analysis: C83H90Cl2F3N11O25.2.5HCl.10H2O

calcd. C: 56.34%, H: 5.13%. N: 8.71%, Cl: 4.01%, F: 3.22%

Found: C: 48.75%, H: 5.36%. N: 7.77%, Cl: 7.68%, F: 2.73%

MS (ESI): 1770[M+3]+, 1768[M+1]−

Example 11

The following compounds were prepared in a similar manner as described above. TABLE 3 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond NHCO bond

CH2 [M + 1]⁻ = 1822 Calcd. for C88H93Cl2N11O28•3.8HCl•14.7H2O C: 47.46%, H: 5.71%, N: 6.92%, Cl: 9.23% Found: C: 47.40%, H: 5.57%, N: 7.14%, Cl: 9.15%

bond CONMe bond

CH2 [M + 1]⁻ = 1837 Calcd. for C89H95Cl2N11O28•2.0HCl•12.0H2O C: 50.26%, H: 5.73%, N: 7.24%, Cl: 6.67% Found: C: 50.21%, H: 5.16%, N: 7.13%, Cl: 6.59%

bond CONMe bond

CH2 [M + 1]⁻ = 1746 Calcd. for C82H89Cl2N11O28•1.8HCl•10.0H2O C: 49.41%, H: 5.60%, N: 7.73%, Cl: 6.76% Found: C: 49.40%, H: 5.38%, N: 7.66%, Cl: 6.70%

bond CONH bond

CH2 [M + 1]⁻ = 1692 Calcd. for C80H85Cl3N10O25•1.9HCl•11.3H2O C: 48.88%, H: 5.61%, N: 7.13%, Cl: 8.84% Found: C: 48.88%, H: 5.48%, N: 7.29%, Cl: 8.81%

bond CONH bond

CH2 [M + 3]⁺ = 1678 [M + 1]⁻ = 1675 Calcd. for C80H85Cl2FN10O25•1.1HCl•8.7H2O C: 51.29%, H: 5.57%, N: 8.48%, Cl: 5.87%, F: 1.01% Found: C: 51.14%, H: 5.86%, N: 8.73%, Cl: 5.83%, F: 0.63%

TABLE 4

bond CONH bond

CH2 [M +1]⁺ =1727 [M +1]⁻ =1725 Calcd. for C81H85Cl2F3N10O25•1.6HCl•8.5H2O C: 50.20%, H: 5.39%, N: 1.23%, Cl: 6.59%, F: 2.94% Found: C: 50.18%, H: 5.37%, N: 7.32%, Cl: 6.60%, F: 2.87%

bond CONH bond

CH2 [M +1]⁻ =1675 Calcd. for C80H85Cl2FN10O25•1.6HCl•9.1H2O C: 50.60%, H: 5.56%, N: 7.38%, Cl: 6.72%, F: 1.00% Found: C: 50.56%, H: 5.47%, N: 7.66%, Cl: 6.81%, F: 1.03%

bond CONH bond

CH2 [M +1]⁻ =1675 Calcd. for C80H85Cl2FN10O25•1.1HCl•10.4H2O C: 50.47%, H: 5.66%, N: 8.36%, Cl: 5.77%, F: 1.00% Found: C: 50.30%, H: 5.81%, N: 8.55%, Cl: 5.85%, F: 0.66%

bond CONH bond

CH2 [M +1]⁻ =1707 Calcd. for C84H88Cl2N10O25•1.7HCl•10.3H2O C: 51.58%, H: 5.68%, N: 7.16%, Cl: 6.71% Found: C: 51.52%, H: 5.57%, N: 7.35%, Cl: 6.76%

bond CONH bond

CH2 M +1]⁻ =1687 Calcd. for C81H88Cl2N10O26•1.8HCl•10.2H2O C: 50.20%, H: 5.73%, N: 7.23%, Cl: 6.95% Found: C: 50.21%, H: 5.56%, N: 7.47%, Cl: 6.90%

bond CONH bond

CH2 [M +3]⁺ =1703 [M +1]⁻ =1701 Calcd. for C82H90Cl2N10O26•2.1HCl•9.6H2O C: 50.45%, H: 5.75%, N: 7.18%, Cl: 7.45% Found: C: 50.39%, H: 5.53%, N: 7.48%, Cl: 7.44%

bond CONH bond

CH2 [M +1]⁻ =1658 Calcd. for C79H85Cl2N11O25•3.0HCl•10.4H2O C: 48.50%, H: 5.61%, N: 7.88%, Cl: 9.06% Found: C: 48.41%, H: 5.46%, N: 8.10%, Cl: 9.12%

bond CONH bond

CH2 [M +1]⁻ =1682 Calcd. for C81H85Cl2N11O25•1.5HCl•10.4H2O C: 50.52%, H: 5.62%, N: 8.00%, Cl: 6.44% Found: C: 50.49%, H: 5.54%, N: 8.13%, Cl: 6.39%

bond CONH bond

CH2 [M +1]⁻ =1759 Calcd. for C87H88Cl2N11O26•1.9HCl•10.2H2O C: 51.89%, H: 5.52%, N: 6.96%, Cl: 6.87% Found: C: 51.81%, H: 5.39%, N: 7.10%, Cl: 6.87%

TABLE 5

bond CONH bond

CH2 [M +1]⁻ =1685 Calcd. for C82H90Cl2N10O25•1.3HCl•9.7H2O C: 51.60%, H: 5.85%, N: 7.34%, Cl: 6.13% Found: C: 51.57%, H: 5.79%, N: 7.39%, Cl: 6.16%

bond CONH bond

CH2 [M +1]⁻ =1726 Calcd. for C80H84Cl4N10O25•1.9HCl•10.4H2O C: 48.43%, H: 5.42%, N: 7.06%, Cl: 10.54% Found: C: 48.43%, H: 5.03%, N: 7.18%, Cl: 10.47%

bond NHCO NH

CH2 [M +1]⁻ =1792 Calcd. for C88H95Cl2N11O26•1.9HCl•8.4H2O C: 52.47%, H: 5.69%, N: 7.65%, Cl: 6.86% Found: C: 52.48%, H: 5.71%, N: 7.70%, Cl: 6.80%

bond CONH bond

CH2 [M +1]⁻ =1693 Calcd. for C80H84Cl2F2N10O25•1.5HCl•8.2H2O C: 50.65%, H: 5.41%, N: 7.38%, Cl: 6.54%, F: 2.00% Found: C: 50.56%, H: 5.09%, N: 7.57%, Cl: 6.56%, F: 1.93%

bond CONH bond

CH2 [M +3]⁺ =1745 [M +1]⁻ =1743 Calcd. for C81H84Cl2F4N10O25•1.9HCl•8.9H2O C: 49.28%, H: 5.29%, N: 7.10%, Cl: 7.00%, F: 3.85% Found: C: 49.21%, H: 5.03%, N: 7.20%, Cl: 6.94%, F: 3.76%

bond CONH bond

CH2 [M +3]⁺ =1713 [M +1]⁻ =1711 Calcd. for C80H83Cl2F3N10O25•1.9HCl•9.3H2O C: 49.29%, H: 5.35%, N: 7.19%, Cl: 7.09%, F: 2.92% Found: C: 49.29%, H: 5.11%, N: 7.27%, Cl: 7.14%, F: 2.77%

bond CONH bond

CH2 [M +1]⁻ =1757 Calcd. for C81H85Cl2F3N10O25S•2.2HCl•8.9H2O C: 48.66%, H: 5.29%, N: 7.01%, Cl: 7.45%, F: 2.85%, S: 1.60% Found: C: 48.64%, H: 5.24%, N: 7.01%, Cl: 7.42%, F: 2.75%, S: 1.61%

bond CONH bond

CH2 [M +3]⁺ =1719 [M +1]⁻ =1717 Calcd. for C82H90Cl2N10O27•1.4HCl•10.7H2O C: 50.19%, H: 5.79%, N: 7.14%, Cl: 6.14% Found: C: 50.15%, H: 5.70%, N: 7.29%, Cl: 6.08%

bond CONH bond

CH2 [M +1]⁻ =1737 Calcd. for C79H84BrCl2N11O25•1.6HCl•10.4H2O C: 47.82%, H: 5.41%, N: 7.77%, Cl: 6.43%, Br: 4.03% Found: C: 47.80%, H: 5.33%, N: 7.81%, Cl: 6.39%, Br: 4.12%

TABLE 6

bond CONH bond

CH2 [M +3]⁺ =1741 [M +1]⁻ =1739 Calcd. for C81H86Cl2F2N10O25S•2.1HCl•9.0H2O C: 49.15%, H: 5.40%, N: 7.08%, Cl: 7.34%, F: 1.92%, S: 1.62% Found: C: 49.18%, H: 5.26%, N: 7.12%, Cl: 7.26%, F: 1.81%, S: 1.63%

bond CONH bond

CH2 [M +1]⁻ =1693 Calcd. for C79H84Cl3N11O25•1.8HCl•11.2H2O C: 48.38%, H: 5.56%, N: 7.86%, Cl: 8.68% Found: C: 48.34%, H: 5.45%, N: 7.78%, Cl: 8.72%

bond CONH bond

CH2 [M +1]⁺ =1768 [M +1]⁻ =1766 Calcd. for C81H87BrCl2N10O26•1.4HCl•10.6H2O C: 48.42%, H: 5.50%, N: 6.97%, Cl: 6.00%, Br: 3.98% Found: C: 48.34%, H: 5.42%, N: 7.09%, Cl: 5.96%, Br: 4.36%

bond CONH bond

CH2 [M +1]⁻ =1731 Calcd. for C83H92Cl2N10O27.1.8HCl.9.7H2O C: 50.53%, H: 5.78%, N: 7.10%, Cl: 6.83% Found: C: 50.53%, H: 5.56%, N: 7.11%, Cl: 6.78%

bond CONH bond

CH2 [M +1]⁻ =1791 Calcd. for C89H96Cl2N10O26•1.5HCl•10.0H2O C: 52.72%, H: 5.84%, N: 6.91%, Cl: 6.12% Found: C: 52.73%, H: 5.81%, N: 6.91%, Cl: 6.12%

bond CONH bond

CH2 [M +1]⁻ =1700 Calcd. for C81H84Cl2FN11O25•1.9HCl•9.4H2O C: 50.14%, H: 5.44%, N: 7.94%, Cl: 7.13%, F: 0.98% Found: C: 49.88%, H: 5.37%, N: 8.24%, Cl: 7.09%, F: 0.93%

bond CONH bond

CH2 [M +3]⁺ =1728 [M +1]⁻ =1726 Calcd. for C80H84Cl4N10O25•1.3HCl•9.8H2O C: 49.24%, H: 5.42%, N: 7.18%, Cl: 9.63% Found: C: 49.21%, H: 5.25%, N: 7.38%, Cl: 9.64%

bond CONH bond

CH2 [M +1]⁻ =1736 Calcd. for C80H84Cl3N11O27•1.2HCl•10.1H2O C: 48.93%, H: 5.41%, N: 7.85%, Cl: 7.58% Found: C: 48.92%, H: 5.32%, N: 7.93%, Cl: 7.60%

bond CONH bond

CH2 [M +1]⁻ =1805 Calcd. for C80H85Cl4N11O27S•1.7HCl•10.6H2O C: 46.66%, H: 5.28%, N: 7.48%, Cl: 9.81%, S: 1.56%

TABLE 7

bond CONH bond

CH2 [M +1]⁻ =1758 Calcd. for C83H87Cl3N12O25•1.1HCl•11.1H2O C: 49.87%, H: 5.56%, N: 8.41%, Cl: 7.27% Found: C: 49.86%, H: 5.45%, N: 8.43%, Cl: 7.25%

bond CONH bond

CH2 [M +3]⁺ =1691 [M +1]⁻ =1689 Calcd. for C81H87Cl2FN10O25•1.8HCl•9.4H2O C: 50.53%, H: 5.63%, N: 7.27%, Cl: 7.00%, F: 0.99% Found: C: 50.52%, H: 5.47%, N: 7.34%, Cl: 7.03%, F: 0.95%

bond CONH bond

CH2 [M +3]⁺ =1769 [M +1]⁻ =1767 Calcd. for C86H90Cl2FN11O25•1.6HCl•8.8H2O C: 52.05%, H: 5.55%, N: 7.76%, Cl: 6.43%, F: 0.96% Found: C: 52.03%, H: 5.57%, N: 7.73%, Cl: 6.44%, F: 0.90%

bond CONH bond

CH2 [M +1]⁻ =1715 Calcd. for C82H88Cl2N10O27•1.4HCl•9.6H2O C: 50.75%, H: 5.64%, N: 7.22%, Cl: 6.21% Found: C: 50.71%, H: 5.50%, N: 7.29%, Cl: 6.13%

bond CONH bond

CH2 [M +3]⁺ =1727 [M +1]⁻ =1725 Calcd. for C81H86Cl2F2N10O26•1.9HCl•8.4H2O C: 49.96%, H: 5.52%, N: 7.19%, Cl: 7.10%, F: 1.95% Found: C: 49.90%, H: 5.25%, N: 7.49%, Cl: 7.10%, F: 1.88%

bond CONH bond

CH2 [M +1]⁻ =1716 Calcd. for C82H88Cl2N10O27•1.3HCl•11.3H2O C: 50.06%, H: 5.73%, N: 7.12%, Cl: 5.95% Found: C: 50.05%, H: 5.58%, N: 7.20%, Cl: 5.99%

bond CONH bond

CH2 [M +3]⁺ =1729 [M +1]⁻ =1727 Calcd. for C83H91Cl2N11O262•2HCl•11.6H2O C: 49.38%, H: 5.81%, N: 7.63%, Cl: 7.38% Found: C: 49.40%, H: 5.57%, N: 7.65%, Cl: 7.33%

bond CONH bond

CH2 [M +3]⁺ =1674 [M +1]⁻ =1672 Calcd. for C80H87Cl2N11O25•1.8HCl•10.8H2O C: 49.69%, H: 5.75%, N: 7.97%, Cl: 6.97% Found: C: 49.67%, H: 5.59%, N: 8.15%, Cl: 6.89%

bond CONH bond

CH2 [M +3]⁺ =1724 [M +1]⁻ =1722 Calcd. for C84H89Cl2N11O25•2.0HCl•10.4H2O C: 50.86%, H: 5.68%. N: 7.77%, Cl: 7.15% Found: C: 50.82%, H: 5.50%, N: 7.96%, Cl: 7.09%

TABLE 8

bond CONH bond

CH2 [M + 3]⁺ = 1716 [M + 1]⁻ = 1714 Calcd. for C81H85Cl2N11O25S•2.2HCl•10.8H2O C: 48.88%, H: 5.51%, N: 7.74%, Cl: 7.48%, S: 1.61% Found: C: 48.85%, H: 5.50%, N: 7.92%, Cl: 7.40%, S: 1.50%

bond NHCO bond

CH2 [M + 1]⁻ = 1775 Calcd. for C88H94Cl2N10O26•1.7HCl•8.9H2O C: 52.82%, H: 5.72%, N: 7.00%, Cl: 6.56% Found: C: 52.79%, H: 5.70%, N: 1.10%, Cl: 6.49%

CH2 NHCO bond

CH2 [M + 3]⁺ = 1793 [M + 1]⁻ = 1791 Calcd. for C89H96Cl2N10O26•1.8HCl•8.4H2O C: 53.19%, H: 5.75%, N: 6.97%, Cl: 6.70% Found: C: 53.12%, H: 5.72%, N: 7.23%, Cl: 6.77%

bond NHCO CH2

CH2 [M + 3]⁺ = 1793 [M + 1]⁻ = 1791 Calcd. for C89H96Cl2N10O26•1.8HCl•9.1H2O C: 52.86%, H: 5.78%, N: 6.93%, Cl: 6.66% Found: C: 52.87%, H: 5.66%, N: 6.83%, Cl: 6.63%

TABLE 9 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemetal Analysis

bond CONH bond

CH2 [M + 3]⁺ = 1659 [M + 1]⁻ = 1657 Calcd. for C80H86Cl2N10O25•2HCl•13H2O C: 48.88%, H: 5.85%, N: 7.13%, Cl: 7.21% Found: C: 49.00%, H: 5.73%, N: 7.35%, Cl: 6.83%

bond CONH bond

CH2 [M + 1]⁻ = 1673 Calcd. for C81H88Cl2N10O25•2HCl•15H2O C: 48.27%, H: 6.00%, N: 6.95%, Cl: 7.04% Found: C: 48.14%, H: 6.05%, N: 7.25%, Cl: 6.86%

bond CONH bond

CH2 [M + 1]⁻ = 1704 Calcd. for C80H85Cl2N11O27•2HCl•11H2O C: 48.66%, H: 5.56%, N: 7.80%, Cl: 7.18% Found: C: 48.80%, H: 5.97%, N: 7.90%, Cl: 6.79%

bond CONH bond

CH2 [M + 1]⁻ = 1687 Calcd. for C81H88Cl2N10O26•2HCl•12H2O C: 49.19%, H: 5.81%, N: 7.08%, Cl: 7.17% Found: C: 49.10%, H: 5.98%, N: 7.57%, Cl: 6.20%

bond CONH bond

CH2 [M + 1]⁻ = 1703 Calcd. for C82H90Cl2N10O26•2HCl•14H2O C: 48.57%, H: 5.97%, N: 6.91%, Cl: 6.99% Found: C: 48.77%, H: 5.88%, N: 7.10%, Cl: 6.60%

bond CONH bond

CH2 [M + 1]⁻ = 1763 Calcd. for C87H92Cl2N10O26•2HCl•9H2O C: 52.25%, H: 5.65%, N: 7.00%, Cl: 7.09% Found: C: 51.97%, H: 5.56%, N: 7.08%, Cl: 7.31%

bond CONH bond

CH2 [M + 1]⁻ = 1777 Calcd. for C88H94Cl2N10O26•3HCl•10H2O C: 51.10%, H: 5.70%, N: 6.77%, Cl: 8.57% Found: C: 51.30%, H: 5.68%, N: 6.94%, Cl: 7.97%

TABLE 10

bond CONH bond

CH2 [M + 1]⁻ = 1810 Calcd for C87H91Cl2N11O28•1HCl•12H2O C: 50.61%, H: 5.67%, N: 7.47%, Cl: 5.16% Found: C: 50.54%, H: 5.50%, N: 7.47%, Cl: 5.55%

bond CONH bond

CH2 [M + 1]⁻ = 1671 Calcd. for C81H88Cl2N10O25•2HCl•9H2O C: 51.00%, H: 5.71%, N: 7.34%, Cl: 7.43% Found: C: 51.04%, H: 5.72%, N: 7.63%, Cl: 6.81%

bond CONH bond

CH2 [M + 3]⁺ = 1683 [M + 1]⁺ = 1661 Calcd. for C81H88Cl2N10O25•2HCl•13H2O C: 49.14%, H: 5.91%, N: 7.08%, Cl: 7.16% Found: C: 48.78%, H: 5.72%, N: 7.24%, Cl: 8.05%

bond CONH bond

CH2 [M + 1]⁻ = 1732 Calcd. for C81H87Cl2N11O28•2HCl•12H2O C: 48.10%, H: 5.63%, N: 7.62%, Cl: 7.01% Found: C: 48.25%, H: 5.66%, N: 7.86%, Cl: 6.75%

bond CONH bond

CH2 [M + 1]⁻ = 1702 Calcd. for C80H85Cl2N11O27•2HCl•12H2O C: 48.22%, H: 5.61%, N: 7.73%, Cl: 7.12% Found: C: 48.17%, H: 5.61%, N: 7.83%, Cl: 6.66%

bond CONH bond

CH2 [M + 1]⁻ = 1702 Calcd. for C80H85Cl2N11O27•2HCl•12H2O C: 48.22%, H: 5.61%, N: 7.73%, Cl: 7.12% Found: C: 48.30%, H: 5.54%, N: 8.05%, Cl: 6.66%

bond CONH bond

CH2 [M + 1]⁻= 1763 Calcd. for C87H92Cl2N10O26•1HCl•13H2O C: 51.34%, H: 5.89%, N: 6.88%, Cl: 5.23% Found: C: 51.04%, H: 5.94%, N: 7.09%, Cl: 5.94%

bond CONH bond

CH2 [M + 1]⁻ = 1763 Calcd. for C87H92Cl2N10O26•2HCl•14H2O C: 50.00%, H: 5.88%, N: 6.70%, Cl: 6.79% Found: C: 49.98%, H: 5.86%, N: 6.98%, Cl: 6.44%

bond CONH bond

CH2 [M + 1]⁻ = 1713 Calcd. for C84H94Cl2N10O25•1.5HCl•9H2O C: 51.28%, H: 6.02%, N: 7.12%, Cl: 6.31% Found: C: 51.21%, H: 5.96%, N: 7.36%, Cl: 6.20%

bond CONH bond

CH2 [M + 1]⁻ = 1691 Calcd. for C80H85Cl3N10O25•0.2HCl•11H2O C: 50.61%, H: 5.69%, N: 7.38%, Cl: 5.98% Found: C: 50.88%, H: 6.08%, N: 7.40%, Cl: 6.15%

TABLE 11

bond CONH bond

CH2 [M +1]⁻ =1659 Calcd. for C18H84Cl2N12O25•1.2HCl•9H2O C: 50.20%, H: 5.57%, N: 9.01%, Cl 6.08% Found: C: 50.39%, H: 5.73%, N: 9.02%, Cl: 6.27%

bond CONH bond

CH2 [M +3]⁺ =1727 [M +1]⁻ =1725 Calcd. for C81H85Cl2F3N10O25•1.3 HCl•10H2O C: 49.79%, H: 5.48%, N: 7.17%, Cl: 5.99%, F: 2.92% Found: C: 49.86%, H: 5.44%, N: 7.36%, Cl: 6.13%, F: 2.81%

bond CONH bond

CH2 [M +3]⁺ =1703 [M +1]⁻ =1701 Calcd. for C81H86Cl2N10O27•2HCl•9H2O C: 50.21%, H: 5.51%, N: 7.23%, Cl: 7.32% Found: C: 50.03%, H: 5.52%, N: 7.31%, Cl: 7.38%

bond CONH bond

CH2 [M +1]⁻ =1800 Calcd. for C87H99Cl2N11O27•2HCl•7H2O C: 52.23%, H: 5.79%, N: 7.70%, Cl: 7.09% Found: C: 52.28%, H: 6.24%, N: 7.96%, Cl: 7.04%

bond CONH bond

CH2 [M +3]⁺ =1665 [M +1]⁻ =1663 Calcd. for C78H84Cl2N10O25S1•2HCl•10H2O C: 48.85%, H: 5.57%, N: 7.30%, Cl: 7.40% Found: C: 49.00%, H: 5.12%, N: 7.37%, Cl: 6.98%

bond CONH bond

CH2 [M +1]⁻ =1790 Calcd. for C89H97Cl2N11O25•1.6 HCl•10.3H2O C: 52.51%, H: 5.90%, N: 7.57%, Cl: 6.27% Found: C: 52.45%, H: 5.56%, N: 7.88%, Cl: 6.16%

bond CONH bond

CH2 [M +1]⁻ =1764 Calcd. for C86H91Cl2N11O26•1.2HCl•9.1H2O C: 52.34%, H: 5.64%, N: 7.81%, Cl: 5.75% Found: C: 52.34%, H: 5.54%, N: 7.84%, Cl: 5.72%

bond CONH bond

CH2 [M +3]⁺ =1660 [M +1]⁻ =1658 Calcd. for C79H85Cl2N11O25•2.5HCl•10.5H2O C: 48.91%, H: 5.64%, N: 7.94%, Cl: 8.22% Found: C: 48.89%, H: 5.49%, N: 8.05%. Cl: 8.17%

bond CONH bond

CH2 [M +3]⁺ =1717 [M +1]⁻ =1715 Calcd. for C82H88Cl2N10O27•2.5 HCl•12.4H2O C: 48.49%, H: 5.72%, N: 6.90%, Cl: 7.85% Found: C: 48.39%, H: 5.50%, N: 7.02%, Cl: 7.91%

bond CONH bond

CH2 [M +3]⁺ =1689 [M +1]⁻ =1687 Calcd. for C81H88Cl2N10O26•2.5HCl•10.2H2O C: 49.55%, H: 5.69%, N: 7.13%, Cl: 8.13% Found: C: 49.47%, H: 5.32%, N: 7.44%, Cl: 8.09%

TABLE 12

bond CONH bond

CH2 [M +3]⁺ =1792 [M +1]⁻ =1790 Calcd. for C88H93Cl2N11O26•1.3HCl•8.7H2O C: 52.96%, H: 5.64%, N: 7.72%, Cl: 5.86% Found: C: 52.95%, H: 5.56%, N: 7.90%, Cl: 5.80%

bond CONH bond

CH2 [M +3]⁺ =1780 [M +1]⁻ =1778 Calcd. for C86H91Cl2N11O26•2.1HCl•9.4H2O C: 51.35%, H: 5.61%, N: 7.66%, Cl: 7.23% Found: C: 51.37%, H: 5.57%, N: 7.58%, Cl: 7.31%

bond CONH bond

CH2 [M +1]⁻ =1783 Calcd. for C88H100Cl2N10O26•1.7 HCl•8.9H2O C: 52.66%, H: 6.00%, N: 6.98%, Cl: 6.54% Found: C: 52.61%, H: 5.84%, N: 7.04%, Cl: 6.44%

bond CONH bond

CH2 [M +1]⁻ =1734 Calcd. for C85H89Cl2N11O25•2.4 HCl•10.4H2O C: 50.78%, H: 5.63%, N: 7.66%, Cl: 7.76% Found: C: 50.76%, H: 5.62%, N: 7.76%, Cl: 7.80%

bond CONH bond

CH2 [M +3]⁺ =1778 [M +1]⁻ =1776 Calcd. for C88H95Cl2N11O25•1.3HCl•8.8H2O C: 53.28%, H: 5.79%, N: 7.77%, Cl: 5.90% Found: C: 53.23%, H: 5.59%, N: 7.96%, Cl: 5.85%

bond CONH bond

CH2 [M +1]⁻ =1869 Calcd. for C94H98Cl2N10O27•1.7HCl•9.7H2O C: 00%, H: 00%, N: 00%, Cl: 00% Found: C: 00%, H: 00%, N: 00%, Cl: 00%

bond CONH bond

CH2 [M +3]⁺ =1781 [M +1]⁻ =1779 Calcd. for C87H92Cl2N10O27•2HCl•9H2O C: 51.84%, H: 5.60%, N: 6.95%, Cl: 7.04% Found: C: 51.89%, H: 5.64%, N: 6.93%, Cl: 6.55%

bond CONH bond

CH2 [M +1]⁻ =1892 Calcd. for C93H103Cl2N11O28•11.6 HCl•2.3H2O C: 51.08%, H: 5.92%, N: 7.05%, Cl: 6.97% Found: C: 51.00%, H: 5.71%, N: 7.21%, Cl: 6.87%

bond CONH bond

CH2 [M +1]⁻ =1748 Calcd. for C86H91Cl2N11O25•1.9 HCl•10.6H2O C: 51.39%, H: 5.72%, N: 7.67%, Cl: 6.88% Found: C: 51.36%, H: 5.48%, N: 7.72%, Cl: 6.80%

bond CONH bond

CH2 [M +1]⁻ =1754 Calcd. for C84H89Cl2N11O27•1.4 HCl•11.4H2O C: 50.14%, H: 5.67%, N: 7.66%, Cl: 5.99% Found: C: 50.14%, H: 5.53%, N: 7.79%, Cl: 6.04%

TABLE 13

bond CONH bond

CH2 [M +1]⁻ =1754 Calcd. for C86H97Cl1N11O25•2.2HCl•12.2H2O C: 50.25%, H: 6.06%, N: 7.50%, Cl: 7.24% Found: C: 50.24%, H: 5.88%, N: 7.59%, Cl: 7.29%

bond CONH bond

CH2 [M +1]⁻ =1737 Calcd. for C84H90Cl2N12O25•1.6HCl•11.3H2O C: 50.43%, H: 5.75%, N: 8.40%, Cl: 6.38% Found: C: 50.40%, H: 5.66%, N: 8.60%, Cl: 6.37%

bond CONH bond

CH2 [M +1]⁻ =1858 Calcd. for C88H93Br1Cl2N10O26•1.5HCl•10.8H2O C: 50.17%, H: 5.55%, N: 6.65%, Cl: 5.89%, Br: 3.79% Found: C: 50.18%, H: 5.40%, N: 6.73%, Cl: 5.82%, Br: 3.84%

bond CONH bond

CH2 [M +3]⁺ =1862 [M +1]⁻ =1860 Calcd. for C93H103Cl2N11O26•1.7HCl•10.1H2O C: 53.05%, H: 5.98%, N: 7.32%, Cl: 6.23% Found: C: 53.02%, H: 5.82%, N: 7.55%, Cl: 6.26%

bond CONH bond

CH2 [M +3]⁺ =1781 [M +1]⁻ =1779 Calcd. for C86H92Cl2N12O26•2HCl•11.1H2O C: 50.30%, H: 5.70%, N: 8.19%, Cl: 6.91% Found: C: 50.21%, H: 5.60%, N: 8.44%, Cl: 6.88%

bond CONH bond

CH2 [M +1]⁻ =1821 Calcd. for C89H94Cl2N10O28•1.8HCl•10.8H2O C: 51.32%, H: 5.68%, N: 6.72%, Cl: 6.47% Found: C: 51.34%, H: 5.45%, N: 6.38%, Cl: 6.36%

bond CONH bond

CH2 [M +3]⁺ =1739 [M +1]⁻ =1737 Calcd. for C84H90Cl2N12O25•1.9HCl•10.6H2O C: 50.47%, H: 5.70%, N: 8.41%, Cl: 6.92% Found: C: 50.38%, H: 5.34%, N: 8.44%, Cl: 6.93%

bond CONH bond

CH2 [M +1]⁻ =1675 Calcd. for C80H85Cl2F1N10O25•1.8HCl•10H2O C: 49.99%, H: 5.60%, N: 7.29%, Cl: 7.01%, F: 0.99% Found: C: 49.96%, H: 5.43%, N: 7.48%, Cl: 7.03%, F: 0.95%

bond CONH bond

CH2 [M +3]⁺ =1742 [M +1]⁻ =1740 Calcd. for C81H86Cl2F3N11O25•2.7HCl•13.4H2O C: 46.74%, H: 5.59%, N: 7.40%, Cl: 8.01%, F: 2.74% Found: C: 46.72%, H: 5.31%, N: 7.54%, Cl: 7.91%. F: 2.51%

bond CONH bond

CH2 [M +1]⁻ =1768 Calcd. for C83H90Cl2F3N11O25•2.8HCl•10.5H2O C: 48.37%, H: 5.57%, N: 7.48%, Cl: 8.26%, F: 2.77% Found: C: 48.20%, H: 5.47%, N: 7.78%, Cl: 8.22%, F: 2.59%

TABLE 14

bond CONH bond

CH2 [M +1]⁻ =1691 Calcd. for C80H85Cl3N10O25•1.6HCl•11.9H2O C: 48.88%, H: 5.66%, N: 7.13%, Cl: 8.30% Found: C: 48.82%, H: 5.39%, N: 7.22%, Cl: 8.22%

bond CONH bond

CH2 [M +3]⁺ =1743 [M +1]⁻ =1741 Calcd. for C81H85Cl2F3N10O26•2.6HCl•8.5H2O C: 48.88%, H: 5.30%, N: 7.04%, Cl: 8.19%, F: 2.86% Found: C: 49.89%, H: 5.28%, N: 7.44%, Cl: 6.78%, F: 2.73%

bond CONH bond

CH2 [M +1]⁻ =1741 Calcd. for C81H85Cl2F3N10O26•2HCl•10H2O C: 48.66%, H: 5.40%, N: 7.01%, Cl: 7.27%, F: 2.85% Found: C: 48.66%, H: 5.27%, N: 7.27%, Cl: 7.20%, F: 2.72%

bond CONH bond

CH2 [M +3]⁺ =1693 [M +1]⁻ =1691 Calcd. for C80H85Cl3N10O25•1.2HCl•11.3H2O C: 49.52%, H: 5.65%, N: 7.22%, Cl: 7.67% Found: C: 49.49%, H: 5.53%, N: 7.41%, Cl: 7.72%

bond CONH bond

CH2 [M +1]⁻ =1736 Calcd. for C80H85Cl2Br1N10O25•1.6HCl•11.6H2O C: 47.93%, H: 5.52%, N: 6.99%, Cl: 6.37%, Br: 3.99% Found: C: 47.93%, H: 5.37%, N: 7.22%, Cl: 6.38%, Br: 3.89%

bond CONH bond

CH2 [M +3]⁺ =1738 [M +1]⁻ =1736 Calcd. for C80H84Cl3N11O27•2.7HCl•8.7H2O C: 48.21%, H: 5.26%, N: 7.73%, Cl: 10.14% Found: C: 48.15%, H: 5.21%, N: 7.97%, Cl: 10.14%

bond CONH bond

CH2 [M +1]⁻ =1725 Calcd. for C80H84Cl4N10O25•1.9HCl•9H2O C: 49.05%, H: 5.35%, N: 7.15%, Cl: 10.68% Found: C: 49.02%, H: 5.26%, N: 7.30%, Cl: 10.68%

bond CONH bond

CH2 [M +3]⁺ =1745 [M +1]⁻ =1743 Calcd. for C81H84Cl2F4N10O25•2.1HCl•10.2H2O C: 48.53%, H: 5.35%, N: 6.99%, Cl: 7.25%, F: 3.79% Found: C: 48.54%, H: 5.38%, N: 7.12%, Cl: 7.18%, F: 3.57%

bond CONH bond

CH2 [M +1]⁻ =1757 Calcd. for C81H85Cl2F3N10O25S1•1.9HCl•11.9H2O C: 47.64%, H: 5.46%, N: 6.86%, Cl: 6.77%, F: 2.79%, S: 1.57% Found: C: 47.62%, H: 5.41%, N: 6.96%, Cl: 6.73%, F: 2.62%, S: 1.41%

bond CONH bond

CH2 [M +3]⁺ =1757 [M +1]⁻ =1755 Calcd. for C82H87Cl2F3N10O26•1.9HCl•11.1H2O C: 48.62%, H: 5.53%, N: 6.91%, Cl: 6.83%, F: 2.81% Found: C: 48.63%, H: 5.40%, N: 6.96%, Cl: 6.88%, F: 2.67%

TABLE 15 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemetal Analysis

bond CONH bond

CH2 [M +1]− =1700 Calcd. for C82H91Cl2N11O25•3HCl•15H2O C: 57.88%, H: 5.39%, N: 7.06%, Cl: 4.17% Found: C: 47.31%, H: 5.71%, N: 7.47%, Cl: 8.80%

bond CONH bond

CH2 [M +1]− =1746 Calcd. for C82H91Cl2N11O25•3HCl•12H2O C: 56.36%, H: 5.13%, N: 8.82%, Cl: 4.06% Found: C: 45.39%, H: 5.77%, N: 7.16%, Cl: 7.89%

bond CONH bond

CH2 [M +1]− =1834 Calcd. for C90H97Cl2N11O27•2HCl•14H2O C: 58.89%, H: 5.33%, N: 8.39%, Cl: 3.86% Found: C: 49.9%, H: 5.69%, N: 6.63%, Cl: 6.75%

bond CONH bond

CH2 [M +3]+ =1822 Calcd. for C90H99Cl2N11O26•3HCl•12H2O C: 59.34%, H: 5.48%, N: 8.46%, Cl: 3.89% Found: C: 50.64%, H: 5.67%, N: 7.23%, Cl: 7.91%

TABLE 16

bond CONH bond

CH2 [M +1]− =1792 Calcd. for C88H95Cl2N11O26•3HCl•11H2O C: 58.93%, H: 5.34%, N: 8.59%, Cl: 3.95% Found: C: 50.51%, H: 5.54%, N: 1.34%, Cl: 8.07%

bond CONH bond

CH2 [M +1]− =1716 Calcd. for C82H91Cl2N11O26•3HCl•11H2O C: 57.34%, H: 5.34%, N: 8.97%, Cl: 4.13% Found: C: 48.66%, H: 5.77%, N: 7.70%, Cl: 8.35%

bond CONH bond

CH2 [M +1]− =1860 Calcd. for C93H10Cl2N11O26•2.5HCl•10H2O C: 60.00%, H: 5.58%, N: 8.28%, Cl: 3.81% Found: 0: 52.46%, H: 5.75%, N: 7.44%, Cl: 7.19%

bond CONH bond

CH2 [M +1]− =1794 Calcd. for C88H95Cl2N11O26•2.5HCl•9.5H2O C: 58.93%, H: 5.34%, N: 8.59%, Cl: 3.95% Found: C: 51.24%, H: 5.57%, N: 7.65%, Cl: 8.10%

bond CONH bond

CH2 [M +3]+ =1780 [M +1]− =1778 Calcd. for C87H93Cl2N11O26•1.5HCl•9H2O C: 58.72%, H: 5.27%, N: 8.66%, Cl: 3.98% Found: C: 52.14%, H: 5.48%, N: 7.9%, Cl: 6.55%

bond CONH bond

CH2 [M +1]− =1728 Calcd. for C83H91Cl2N11O26•1.5HCl•10H2O C: 57.64%, H: 5.30%, N: 8.91%, Cl: 4.10% Found: C: 50.71%, H: 5.65%, N: 8.00%, Cl: 6.62%

bond CONH bond

CH2 [M +1]− =1820 Calcd. for C89H95Cl2N11O26•2HCl•10H2O C: 58.68%, H: 5.26%, N: 8.46%, Cl: 3.89% Found: C: 51.56%, H: 5.53%, N: 7.64%, Cl: 6.76%

TABLE 17

bond CONH bond

CH2 [M +3]+ =1808 [M +1]− =1806 Calcd. for C89H97Cl2N11O26•2HCl•10H2O C: 59.13%, H: 5.41%, N: 8.52%, Cl: 3.92% Found: C: 51.96%, H: 5.64%, N: 7.56%, Cl: 7.00%

bond CONH bond

CH2 [M +1]− =1792 Calcd. for C88H95Cl2N11O26•1.5HCl•10H2O C: 58.93%, H: 5.34%, N: 8.59%, Cl: 3.95% Found: C: 52.01%, H: 5.60%, N: 7.68%, Cl: 6.41%

bond CONH bond

CH2 [M +1]− =1754 Calcd. for C86H97Cl2N11O25•3HCl•10H2O C: 58.83%, H: 5.57%, N: 8.78%, Cl: 4.04% Found: C: 50.64%, H: 5.74%, N: 7.91%, Cl: 8.27%

bond CONH bond

CH2 [M +3]+ =1770 [M +1]− =1768 Calcd. for C83H90Cl2F3N11O25•2.5HCl•10H2O C: 56.34%, H: 5.13%, N: 8.71%, Cl: 4.01%, F: 3.22% Found: C: 48.75%, H: 5.36%, N: 7.77%, Cl: 7.68%, F: 2.73%

bond CONH bond

CH2 [M +1]− =1806 Calcd. for C89H97Cl2N11O26•2HCl•9.5H2O C: 59.13%, H: 5.41%, N: 8.52%, Cl: 3.92% Found: C: 51.92%, H: 5.79%, N: 7.60%, Cl: 7.31%

bond CONH bond

CH2 [M +3]+ =1742 [M +1]− =1740 Calcd. for C81H86Cl2F3N11O25•1.5HCl•9.5H2O C: 55.86%, H: 4.98%, N: 8.85%, Cl: 4.07%, F: 3.27% Found: C: 49.44%, H: 5.43%, N: 7.87%, Cl: 6.01%, F: 2.66%

bond CONH bond

CH2 [M +1]− =1737 Calcd. for C84H90Cl2N12O25•3HCl•11H2O C: 58.03%, H: 5.22%, N: 9.67%, Cl: 4.08% Found: C: 49.26%, H: 5.65%, N: 8.33%, Cl: 8.46%

TABLE 18

bond CONH bond

CH2 [M +1]− =1808 Calcd. for C86H94Cl2F3N11O25•2.5HCl•11.5H2O C: 57.08%, H: 5.24%, N: 8.51%, Cl: 3.92%, F: 3.15% Found: C: 48.83%, H: 5.54%, N: 7.33%, Cl: 7.86%, F: 2.73%

bond CONH bond

CH2 [M +3]− =1780 Calcd. for C87H93Cl2N11O26•1.5HCl•10H2O C: 58.72%, H: 5.27%, N: 8.66%, Cl: 3.98% Found: C: 51.85%, H: 5.60%, N: 8.07%, Cl: 5.80%

TABLE 19 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemetal Analysis

bond CONH bond

CH2 [M + 1]⁻ = 1712 Calcd. for C82H87Cl2N11O26•1.3HCl•8.7H2O C: 51.36%, H: 5.56%, N: 8.03%, Cl: 6.10% Found: C: 51.34%, H: 5.62%, N: 8.19%, Cl: 6.03%

bond CONH bond

CH2 [M + 1]⁻ = 1728 Calcd. for C88H91Cl2N11O26•1.8HCl•8.9H2O C: 52.44%, H: 5.53%, N: 7.64%, Cl: 6.68% Found: C: 52.41%, H: 5.49%, N: 7.66%, Cl: 6.75%

bond CONH bond

CH2 [M + 1]⁻ = 1789 Calcd. for C88H91Cl2N11O26•2.0HCl•9.5H2O C: 51.97%, H: 5.55%, N: 7.58%, Cl: 6.97% Found: C: 51.97%, H: 5.44%, N: 7.65%, Cl: 7.07%

TABLE 20

bond CONH bond

CH2 [M + 3]⁺ = 1745 Calcd. for C81H84Cl2N10O25•1.5HCl•9.2H2O C: 49.51%, H: 5.33%, N: 7.13%, Cl: 6.32%, F: 3.87% Found: C: 49.50%, H: 5.28%, N: 7.39%, Cl: 6.37%, F: 3.93%

bond CONH bond

CH2 [M + 3]⁺ = 1694 [M + 1]⁻ = 1692 Calcd. for C80H85Cl2N10O26•1.3HCl•11.2H2O C: 49.49%, H: 5.64%, N: 7.21%, Cl: 6.03%, F: 0.98% Found: C: 49.48%, H: 5.43%, N: 7.27%, Cl: 5.90%, F: 0.91%

bond CONH bond

CH2 [M + 1]⁻ = 1727 Calcd. for C80H84Cl2F3N11O25•1.5HCl•10.2H2O C: 48.88%, H: 5.43%, N: 7.84%, Cl: 6.31%, F: 2.90 Found: C: 48.90%, H: 5.42%, N: 7.94%, Cl: 6.18%, F: 2.76

bond CONH bond

CH2 [M + 1]⁻ = 1754 Calcd. for C80H84BrCl2FN10O25•1.8HCl•9.4H2O C: 48.28%, H: 5.30%, N: 7.04%, Br: 4.01, Cl: 6.77%, F: 0.95 Found: C: 48.26%, H: 5.29%, N: 7.07%, Br: 3.63, Cl: 6.75%, F: 0.90

bond CONH bond

CH2 [M + 3]⁺ = 1716 [M + 1]⁻ = 1714 Calcd. for C83H93Cl2N11O25•2.0HCl•9.5H2O C: 50.87%, H: 5.86%, N: 7.86%, Cl: 7.24% Found: C: 50.86%, H: 5.73%, N: 8.02%, Cl: 7.28%

TABLE 21

bond CONH bond

CH2 [M + 1]⁻ = 1720 Calcd. for C80H84Cl2FN11O27•1.6HCl•10.2H2O C: 48.93%, H: 5.44%, N: 7.85%, Cl: 6.50%, F: 0.97 Found: C: 48.90%, H: 5.28%, N: 8.11%, Cl: 6.46%, F: 0.86

bond CONH bond

CH2 [M + 1]⁻ = 1786 Calcd. for C83H89Cl2F3N10O27•2.0HCl•9.0H2O C: 49.31%, H: 5.43%, N: 6.93%, Cl: 7.01%, F: 2.82 Found: C: 49.30%, H: 5.31%, N: 7.05%, Cl: 7.04%, F: 2.73

bond CONH bond

CH2 [M + 1]⁻ = 1785 Calcd. for C88H92Cl3N11O25•1.9HCl•10.0H2O C: 50.75%, H: 5.64%, N: 7.57%, Cl: 8.53% Found: C: 50.70%, H: 5.43%, N: 7.82%, Cl: 8.50%

bond CONH bond

CH2 [M + 3]⁺ = 1718 Calcd. for C82H91Cl2N11O26•1.4HCl•10.6H2O C: 50.26%, H: 5.84%, N: 7.86%, Cl: 6.15% Found: C: 50.27%, H: 5.61%, N: 7.89%, Cl: 6.20%

bond CONH bond

CH2 [M + 3]⁺ = 1687 [M + 1]⁻ = 1685 Calcd. for C82H90Cl2N10O25•1.5HCl•10.9H2O C: 50.83%, H: 5.89%, N: 7.23%, Cl: 6.40% Found: C: 50.77%, H: 5.69%, N: 7.46%, Cl: 6.33%

TABLE 22

bond CONH bond

CH2 [M + 1]⁻ = 1711 Calcd. for C80H83Cl2F3N10O25•1.6HCl•10.2H2O C: 49.16%, H: 5.41%, N: 7.17%, Cl: 6.53%, F: 2.92 Found: C: 49.18%, H: 5.36%, N: 7.27%, Cl: 6.48%, F: 2.82

bond CONH bond

CH2 [M + 3]⁺ = 1687 [M + 1]⁻ = 1685 Calcd. for C82H90Cl2N10O25•1.5HCl•10.2H2O C: 51.16%, H: 5.86%, N: 7.28%, Cl: 6.45% Found: C: 51.17%, H: 5.80%, N: 7.71%, Cl: 6.37%

bond CONH bond

CH2 [M + 3]⁺ = 1772 [M + 1]⁻ = 1770 Calcd. for C80H84BrCl3N10O25•1.6HCl•10.3H2O C: 47.67%, H: 5.31%, N: 6.95%, Cl: 8.09%, Br: 3.96% Found: C: 47.59%, H: 5.24%, N: 7.20%, Cl: 8.15%, Br 3.84%

bond CONH bond

CH2 [M + 3]⁺ = 1742 [M + 1]⁻ = 1740 Calcd. for C83H91Cl2N13O25•1.2HCl•11.3H2O C: 50.12%, H: 5.82%, N: 9.16%, Cl: 5.70% Found: C: 50.07%, H: 5.67%, N: 9.29%, Cl: 5.70%

bond CONH bond

CH2 [M + 1]⁻ = 1754 Calcd. for C80H86Cl2FN11O27S•2.0HCl•10.6H2O C: 47.58%, H: 5.45%, N: 7.63%, Cl: 7.02%, F: 0.94%, S: 1.59% Found: C: 47.53%, H: 5.30%, N: 7.73%, Cl: 6.99%, F: 0.91%, S: 1.62%

TABLE 23

bond CONH bond

CH2 [M + 3]⁺ = 1742 [M + 1]⁻ = 1740 Calcd. for C84H92Cl2N12O25•1.7HCl•10.9H2O C: 50.47%, H: 5.82%, N: 8.41%, Cl: 6.56% Found: C: 50.30%, H: 5.63%, N: 9.22%, Cl: 6.61%

bond CONH bond

CH2 [M + 3]⁺ = 1695 [M + 1]⁻ = 1693 Calcd. for C80H84Cl2F2N10O25•1.7HCl•10.7H2O C: 49.29%, H: 5.54%, N: 7.19%, Cl: 6.73%, F: 1.95% Found: C: 49.30%, H: 5.42%, N: 7.33%, Cl: 6.67%, F: 1.92%

bond CONH bond

CH2 [M + 3]⁺ = 1709 [M + 1]⁻ = 1707 Calcd. for C81H86Cl2F2N10O25•2.0HCl•8.9H2O C: 50.10%, H: 5.49%, N: 7.21%, Cl: 7.30%, F: 1.96% Found: C: 50.10%, H: 5.53%, N: 7.29%, Cl: 7.21%, F: 1.86%

bond CONH bond

CH2 [M + 1]⁻ = 1784 Calcd. for C84H89Cl2N13O27•2.2HCl•8.3H2O C: 50.11%, H: 5.40%, N: 9.04%, Cl: 7.40% Found: C: 50.09%, H: 5.36%, N: 9.22%, Cl: 7.43%

bond CONH bond

CH2 [M + 3]⁺ = 1660 Calcd. for C79H85Cl2N11O25•2.1HCl•10.0H2O C: 49.52%, H: 5.63%, N: 8.04%, Cl: 7.59% Found: C: 49.48%, H: 5.43%, N: 8.10%, Cl: 7.58%

TABLE 24 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemetal Analysis

bond CONH bond

CH2CH2 [M + 3]+ = 1794 [M + 1]− = 1792 Calcd. for C89H96Cl2N10O26•2.5HCl•10.0H2O C: 51.79%, H: 5.79%, N: 6.79%, Cl: 7.73% Found: C: 51.74%, H: 5.73%, N: 6.91%, Cl: 7.76%

bond CONH bond

CH2CH2 CH2 [M + 3]+ = 1808 [M + 1]− = 1806 Calcd. for C90H98Cl2N10O26•2.3HCl•9.3H2O C: 52.52%, H: 5.82%, N: 6.81%, Cl: 7.41% Found: C: 52.49%, H: 5.64%, N: 6.84%, Cl: 7.34%

bond CONH bond

CH2CH2 CH2 [M + 3]+ = 1853 [M + 1]− = 1851 Calcd. for C90H97Cl2N11O28•1.9HCl•9.6H2O C: 51.62%, H: 5.68%, N: 7.36%, Cl: 6.60% Found: C: 51.59%, H: 5.47%, N: 7.43%, Cl: 6.52%

bond CONH bond

CH2 [M + 3]+ = 1727 [M + 1]− = 1725 Calcd. for C81H85Cl2F3N10O25•1.7HCl•10.4H2O C: 49.24%, H: 5.48%, N: 7.09%, Cl: 6.64%, F: 2.88% Found: C: 49.21%, H: 5.34%, N: 7.22%, Cl: 6.55%, F: 2.88%

TABLE 25

bond CONH bond

CH2 [M + 3]+ = 1693 [M + 1]− = 1691 Calcd. for C80H85Cl3N10O25•1.9HCl•9.3H2O C: 49.79%, H: 5.51%, N: 7.26%, Cl: 9.00% Found: C: 49.77%, H: 5.35%, N: 7.21%, Cl: 9.00%

bond CONH bond

CH2 [M + 3]+ = 1743 [M + 1]− = 1741 Calcd. for C81H85Cl2F3N10O26•1.8HCl•9.8H2O C: 49.02%, H: 5.40%, N: 7.06%, Cl: 6.79%, F: 2.87% Found: C: 49.03%, H: 5.33%, N: 7.24%, Cl: 6.87%, F: 2.79%

bond CONH bond

CH2 [M + 3]+ = 1743 [M + 1]− = 1741 Calcd. for C81H85Cl2F3N10O26•1.7HCl•10.0H2O C: 49.02%, H: 5.42%, N: 7.06%, Cl: 6.61%, F: 2.87% Found: C: 48.98%, H: 5.18%, N: 7.21%, Cl: 6.61%, F: 2.78%

bond CONH bond

CH2 [M + 3]+ = 1761 [M + 1]− = 1759 Calcd. for C81H84Cl3F3N10O25•1.3HCl•9.7H2O C: 49.06%, H: 5.32%, N: 7.06%, Cl: 7.69%, F: 2.87% Found: C: 48.99%, H: 5.13%, N: 7.32%, Cl: 7.72%, F: 2.77%

bond CONH bond

CH2 [M + 1]− = 1735 Calcd. for C80H85BrCl2N10O25•1.8HCl•10.4H2O C: 48.27%, H: 5.45%, N: 7.04%, Br: 4.01%, Cl: 6.77% Found: C: 48.56%, H: 5.22%, N: 7.16%, Br: 3.71%, Cl: 6.83%

bond CONH bond

CH2 [M + 1]− = 1725 Calcd. for C80H84Cl4N10O25•1.7HCl•9.7H2O C: 48.92%, H: 5.39%, N: 7.13%, Cl: 10.29% Found: C: 48.92%, H: 5.23%, N: 7.18%, Cl: 10.30%

bond CONH bond

CH2 [M + 1]− = 1736 Calcd for C80H85BrCl2N10O25•1.9HCl•9.4H2O C: 48.63%, H: 5.39%, N: 7.09%, Br: 4.04%, Cl: 7.00% Found: C: 48.58%, H: 5.24%, N: 7.18%, Br: 3.91%, Cl: 7.01%

bond CONH bond

CH2 [M + 1]− = 1702 Calcd. for C81H86Cl2N10O27•1.2HCl•9.9H2O C: 50.55%, H: 5.60%, N: 7.28%, Cl: 5.89% Found: C: 50.55%, H: 5.49%, N: 7.42%, Cl: 5.94%

TABLE 26

bond CONH bond

CH2 [M + 3]+ = 1689 [M + 1]− = 1687 Calcd for C81H88Cl2N10O26•1.2HCl•10.4H2O C: 50.68%, H: 5.78%, N: 7.30%, Cl: 5.91% Found: C: 50.67%, H: 5.63%, N: 7.32% Cl: 5.84%

bond CONH bond

CH2 [M + 3]+ = 1703 [M + 1]− = 1701 Calcd. for C82H90Cl2N10O26•1.7HCl•8.1H2O C: 51.55%, H: 5.69%, N: 7.33%, Cl: 6.87% Found: C: 51.55%, H: 5.71%, N: 7.42%, Cl: 6.92%

bond CONH bond

CH2 [M + 1]− = 1742 Calcd. for C81H85Cl2F3N10O26•2.0HCl•10.8H2O C: 48.40%, H: 5.45%, N: 6.97%, Cl: 7.06%, F: 2.84% Found: C: 48.38%, H: 5.28%, N: 7.17%, Cl: 7.05%, F: 2.70%

bond CONH bond

CH2 [M + 3]+ = 1691 [M + 1]− = 1689 Calcd. for C81H87Cl2FN10O25•1.2HCl•10.5H2O C: 50.58%, H: 5.72%, N: 7.28%, Cl: 5.90%, F: 0.99% Found: C: 50.54%, H: 5.58%, N: 7.37%, Cl: 5.89%, F: 0.95%

bond CONH bond

CH2 [M + 1]− = 1736 Calcd. for C80H85BrCl2N10O25•1.9HCl•10.2H2O C: 48.27%, H: 5.43%, N: 7.04%, Br: 4.01%, Cl: 6.95% Found: C: 48.27%, H: 5.25%, N: 7.07%, Br: 3.85%, Cl: 6.98%

bond CONH bond

CH2 [M + 1]− = 1694 Calcd. for C80H84Cl2F2N10O25•1.6HCl•10.1H2O C: 49.66%, H: 5.51%, N: 7.24%, Cl: 6.60%, F: 1.96% Found: C: 49.59%, H: 5.50%, N: 7.37%, Cl: 6.65%, F: 1.88%

bond CONH bond

CH2 [M + 3]+ = 1687 [M + 1]− = 1685 Calcd. for C82H90Cl2N10O25•1.2HCl•11.1H2O C: 51.02%, H: 5.92%, N: 7.26%, Cl: 5.88% Found: C: 50.99%, H: 5.74%, N: 7.53%, Cl: 5.95%

bond CONH bond

CH2 [M + 1]− = 1707 Calcd. for C80H86Cl3N11O25•1.8HCl•10.6H2O C: 48.91%, H: 5.59%, N: 7.84%, Cl: 8.66% Found: C: 48.87%, H: 5.40%, N: 7.95%, Cl: 8.62%

TABLE 27

bond CONH bond

CH2 [M + 3]+ = 1745 [M + 1]− = 1743 Calcd. for C81H84Cl2F4N10O25•1.7HCl•9.3H2O C: 49.28%, H: 5.33%, N: 7.10%, Cl: 6.65%, F: 3.85% Found: C: 49.24%, H: 5.24%, N: 7.31%, Cl: 6.66%, F: 3.63%

bond CONH bond

CH2 [M + 1]− = 1709 Calcd. for C80H84Cl3FN10O25•1.9HCl•8.3H2O C: 49.79%, H: 5.35%, N: 7.26%, Cl: 9.00%, F: 0.98% Found: C: 49.78%, H: 5.27%, N: 7.22%, Cl: 8.93%, F: 0.89%

bond CONH bond

CH2 [M + 1]− = 1709 Calcd. for C80H84Cl3FN10O25•1.2HCl•8.9H2O C: 50.17%, H: 5.42%, N: 7.31%, Cl: 7.78%, F: 0.99% Found: C: 50.14%, H: 5.31%, N: 7.49%, Cl: 7.81%, F: 0.87%

bond CONH bond

CH2 [M + 3]+ = 1724 [M + 1]− = 1722 Calcd. for C80H86Cl3N11O26•1.2HCl•9.1H2O C: 49.74%, H: 5.50%, N: 7.98%, Cl: 7.71% Found: C: 49.72%, H: 5.49%, N: 8.04%, Cl: 7.69%

bond CONH bond

CH2 [M + 1]− = 1763 Calcd. for C82H89Cl2N11O29•1.8HCl•3.3H2O C: 52.15%, H: 5.20%, N: 8.16%, Cl: 7.13% Found: C: 52.14%, H: 5.84%, N: 8.29%, Cl: 7.12%

bond CONH bond

CH2 [M + 1]− = 1788 Calcd. for C80H85Cl3FN11O27S•1.6HCl•10.9H2O C: 46.99%, H: 5.34%, N: 7.54%, Cl: 7.98%, F: 0.93%, S: 1.57% Found: C: 46.99%, H: 5.22%, N: 7.64%, Cl: 8.00%, F: 0.81%, S: 1.41%

bond CONH bond

CH2 [M + 1]− = 1743 Calcd. for C81H84Cl2F4N10O25•1.6HCl•7.7H2O C: 50.11%, H: 5.24%, N: 7.21%, Cl: 6.57%, F: 3.91% Found: C: 50.11%, H: 5.27%, N: 7.30%, Cl: 6.62%, F: 3.79%

bond CONH bond

CH2 [M + 3]+ = 1711 [M + 1]− = 1709 Calcd. for C80H84Cl3FN10O25•1.3HCl•9.4H2O C: 49.85%, H: 5.44%, N: 7.27%, Cl: 7.91%, F: 0.99% Found: C: 49.74%, H: 5.15%, N: 7.50%, Cl: 7.79%, F: 1.03%

TABLE 28

bond CONH bond

CH2 [M + 3]+ = 1722 [M + 1]− = 1720 Calcd. for C80H84Cl2FN11O27•1.4HCl•11.0H2O C: 48.76%, H: 5.49%, N: 7.82%, Cl: 6.12%, F: 0.96% Found: C: 48.63%, H: 4.82%, N: 7.99%, Cl: 6.14%, F: 0.90%

bond CONH bond

CH2 [M + 1]− = 1761 Calcd. for C82H88Cl3N13O25•1.2HCl•9.0H2O C: 50.05%, H: 5.49%, N: 9.25%, Cl: 7.57% Found: C: 50.14%, H: 5.52%, N: 8.72%, Cl: 7.60%

bond CONH bond

CH2 [M + 1]− = 1769 Calcd. for C80H84BrCl3N10O25•1.3HCl•10.3H2O C: 47.93%, H: 5.32%, N: 6.99%, Br: 3.99%, Cl: 7.60% Found: C: 47.84%, H: 5.13%, N: 7.10%, Br: 4.06%, Cl: 7.50%

bond CONH bond

CH2 [M + 1]− = 1775 Calcd. for C81H84Cl3F3N10O26•2.0HCl•8.7H2O C: 48.48%, H: 5.19%, N: 6.98%, Cl: 8.83%, F: 2.84% Found: C: 48.49%, H: 5.03%, N: 6.94%, Cl: 8.74%, F: 2.69%

bond CONH bond

CH2 [M + 1]− = 1770 Calcd. for C81H87Cl3N10O27S•2.1HCl•11.8H2O C: 47.22%, H: 5.51%, N: 6.80%, Cl: 8.78%, S: 1.56% Found: C: 47.23%, H: 5.29%, N: 6.89%, Cl: 8.75%, S: 1.49%

bond CONH bond

CH2 [M + 3]+ = 1694 [M + 1]− = 1692 Calcd. for C80H85Cl2FN10O26•1.7HCl•9.1H2O C: 50.09%, H: 5.51%, N: 7.30%, Cl: 6.84%, F: 0.99% Found: C: 50.07%, H: 5.27%, N: 7.31%, Cl: 6.89%, F: 1.05%

bond CONH bond

CH2 [M + 3]+ = 1694 [M + 1]− = 1692 Calcd. for C79H84Cl3N11O25•1.6HCl•11.0H2O C: 48.65%, H: 5.56%, N: 7.90%, Cl: 8.36% Found: C: 48.61%, H: 5.53%, N: 8.07%, Cl: 8.39%

bond CONH bond

CH2 [M + 1]− = 1717 Calcd. for C81H87Cl2N11O27•1.1HCl•1.2H2O C: 49.65%, H: 5.68%, N: 7.86%, Cl: 5.61% Found: C: 49.64%, H: 5.50%, N: 7.98%, Cl: 5.66%

TABLE 29

bond CONH bond

CH2 [M + 1]− = 1719 Calcd. for C81H89Cl2N11O27•1.3HCl•10.6H2O C: 49.69%, H: 5.74%, N: 7.87%, Cl: 5.98% Found: C: 49.62%, H: 5.50%, N: 8.10%, Cl: 5.89%

bond CONH bond

CH2 [M + 3]+ = 1740 [M + 1]− = 1738 Calcd. for C84H89Cl2N11O26•2.3HCl•10.5H2O C: 50.13%, H: 5.62%, N: 7.66%, Cl: 7.57% Found: C: 50.13%, H: 5.49%, N: 7.70%, Cl: 7.57%

bond CONH bond

CH2 [M + 1]− = 1760 Calcd. for C82H88Cl2N12O28•1.4HCl•11.1H2O C: 48.96%, H: 5.59%, N: 8.36%, Cl: 5.99% Found: C: 48.91%, H: 5.46%, N: 8.48%, Cl: 6.02%

bond CONH bond

CH2 [M + 1]− = 1754 Calcd. for C82H85Cl2F3N10O26•1.3HCl•10.8H2O C: 49.33%, H: 5.45%, N: 7.02%, Cl: 5.86%, F: 2.85% Found: C: 49.27%, H: 5.50%, N: 7.20%, Cl: 5.94%, F: 2.71%

bond CONH bond

CH2 [M + 3]+ = 1787 [M + 1]− = 1785 Calcd. for C85H91Cl2N11O26S•1.8HCl•9.3H2O C: 50.57%, H: 5.56%, N: 7.63%, Cl: 6.67%, S: 1.59% Found: C: 50.65%, H: 5.51%, N: 7.29%, Cl: 6.65%, S: 1.61%

bond CONH bond

CH2 [M + 1]− = 1702 Calcd. for C82H90Cl2N10O26•1.5HCl•9.9H2O C: 50.88%, H: 5.80%, N: 7.24%, Cl: 6.41% Found: C: 50.86%, H: 5.80%, N: 7.46%, Cl: 6.48%

bond CONH bond

CH2 [M + 3]+ = 1687 [M + 1]− = 1685 Calcd. for C82H90Cl2N10O25•1.9HCl•10.5H2O C: 50.64%, H: 5.85%, N: 7.20%, Cl: 7.11% Found: C: 50.61%, H: 5.85%, N: 7.40%, Cl: 7.11%

bond CONH bond

CH2 [M + 1]− = 1725 Calcd. for C80H84Cl4N10O25•1.8HCl•10.2H2O C: 48.61%, H: 5.42%, N: 7.09%, Cl: 10.40% Found: C: 48.61%, H: 5.31%, N: 7.19%, Cl: 10.32%

TABLE 30

bond CONH bond

CH2 [M + 1]− = 1686 Calcd. for C82H90Cl2N10O25•2.0HCl•11.1H2O C: 50.26%, H: 5.87%, N: 7.15%, Cl: 7.24% Found: C: 50.20%, H: 5.67%, N: 7.33%, Cl: 7.18%

bond CONH bond

CH2 [M + 1]− = 1699 Calcd. for C83H92Cl2N10O25•1.9HCl•10.7H2O C: 50.79%, H: 5.92%, N: 7.14%, Cl: 7.05% Found: C: 50.74%, H: 5.72%, N: 7.36%, Cl: 6.97%

bond CONH bond

CH2 [M + 1]− = 1689 Calcd. for C81H87Cl2FN10O25•1.8HCl•9.6H2O C: 50.43%, H: 5.64%, N: 7.26%, Cl: 6.98%, F: 0.98% Found: C: 50.37%, H: 5.47%, N: 7.47%, Cl: 7.01%, F: 0.97%

bond CONH bond

CH2 [M + 1]− = 1735 Calcd. for C80H85BrCl2N10O25•1.8HCl•17.2H2O C: 45.48%, H: 5.78%, N: 6.63%, Br: 3.78%, Cl: 6.38% Found: C: 45.45%, H: 5.59%, N: 6.77%, Br: 3.90%, Cl: 6.37%

bond CONH bond

CH2 [M + 1]− = 1707 Calcd. for C84H88Cl2N10O25•1.5HCl•10.1H2O C: 51.87%, H: 5.68%, N: 7.20%, Cl: 6.38% Found: C: 51.84%, H: 5.41%, N: 7.30%, Cl: 6.44%

bond CONH bond

CH2 [M + 1]− = 1726 Calcd. for C81H85Cl2F3N10O25•1.9HCl•12.1H2O C: 48.31%, H: 5.56%, N: 6.96%, Cl: 6.87%, F: 2.83% Found: C: 48.22%, H: 5.30%, N: 7.25%, Cl: 6.81%, F: 2.71%

bond CONH bond

CH2 [M + 1]− = 1675 Calcd. for C80H85Cl2FN10O25•1.7HCl•10.9H2O C: 49.66%, H: 5.65%, N: 7.24%, Cl: 6.78%, F: 0.98% Found: C: 49.72%, H: 5.57%, N: 6.97%, Cl: 6.77%, F: 0.83%

bond CONH bond

CH2 [M + 1]− = 1750 Calcd. for C85H89Cl2N11O26•1.7HCl•10.7H2O C: 50.88%, H: 5.63%, N: 7.68%, Cl: 6.54% Found: C: 50.80%, H: 5.48%, N: 7.82%, Cl: 6.55%

TABLE 31

bond CONH bond

CH2 [M + 1]− = 1778 Calcd. for C87H90Cl2N10O27•1.7HCl•10.7H2O C: 51.39%, H: 5.61%, N: 6.89%, Cl: 6.45% Found: C: 51.40%, H: 5.54%, N: 6.81%, Cl: 6.38%

bond CONH bond

CH2 [M + 3]+ = 1767 [M + 1]− = 1765 Calcd. for C81H87BrCl2N10O26•1.7HCl•10.8H2O C: 48.07%, H: 5.49%, N: 6.92%, Br: 3.95%, Cl: 6.48% Found: C: 48.02%, H: 5.34%, N: 7.15%, Br: 4.17%, Cl: 6.46%

bond CONH bond

CH2 [M + 1]− = 1748 Calcd. for C83H92Cl2N10O28•1.8HCl•10.2H2O C: 49.90%, H: 5.76%, N: 7.01%, Cl: 6.74% Found: C: 49.87%, H: 5.67%, N: 7.15%, Cl: 6.79%

bond CONH bond

CH2 [M + 3]+ = 1794 [M + 1]− = 1792 Calcd. for C89H96Cl2N10O26•1.4HCl•11.2H2O C: 52.26%, H: 5.90%, N: 6.85%, Cl: 5.89% Found: C: 52.24%, H: 5.83%, N: 7.01%, Cl: 5.80%

bond CONH bond

CH2 [M + 1]− = 1748 Calcd. for C83H92Cl2N10O28•2.0HCl•9.2H2O C: 50.16%, H: 5.70%, N: 7.05%, Cl: 7.14% Found: C: 50.14%, H: 5.67%, N: 7.23%, Cl: 7.13%

bond CONH bond

CH2 [M + 1]− = 1746 Calcd. for C84H94Cl2N10O27•1.9HCl•10.3H2O C: 50.41%, H: 5.87%, N: 7.00%, Cl: 6.91% Found: C: 50.39%, H: 5.84%, N: 7.10%, Cl: 6.90%

bond CONH bond

CH2 [M + 1]− = 1749 Calcd. for C86H91Cl2N11O25•2.2HCl•12.6H2O C: 50.22%, H: 5.80%, N: 7.49%, Cl: 7.24% Found: C: 50.20%, H: 5.69%, N: 7.60%, Cl: 7.26%

bond CONH bond

CH2 [M + 1]− = 1750 Calcd. for C86H90Cl2N10O26•1.7HCl•10.1H2O C: 51.79%, H: 5.65%, N: 7.02%, Cl: 6.58% Found: C: 51.80%, H: 5.52%, N: 6.81%, Cl: 6.65%

TABLE 32

bond CONH bond

CH2 [M + 1]− = 1716 Calcd. for C83H92Cl2N10O26•1.8HCl•11.1H2O C: 50.29%, H: 5.90%, N: 7.07%, Cl: 6.80% Found: C: 50.27%, H: 5.82%, N: 7.22%, Cl: 6.81%

bond CONH bond

CH2 [M + 1]− = 1772 Calcd. for C84H89Cl3N12O25•1.2HCl•11.4H2O C: 49.89%, H: 5.63%, N: 8.31%, Cl: 7.36% Found: C: 49.85%, H: 5.64%, N: 8.39%, Cl: 7.29%

bond CONH bond

CH2 [M + 1]− = 1744 Calcd. for C81H84Cl2F4N10O25•1.9HCl•10.2H2O C: 48.70%, H: 5.36%, N: 7.01%, Cl: 6.92%, F: 3.80% Found: C: 48.72%, H: 5.34%, N: 7.18%, Cl: 6.90%, F: 3.52%

bond CONH bond

CH2 [M + 3]+ = 1691 [M + 1]− = 1689 Calcd. for C81H87Cl2FN10O25•1.5HCl•9.1H2O C: 50.96%, H: 5.63%, N: 7.34%, Cl: 6.50%, F: 1.00% Found: C: 50.96%, H: 5.55%, N: 7.69%, Cl: 6.47%, F: 0.95%

bond CONH bond

CH2 [M + 1]− = 1739 Calcd. for C81H86Cl2F2N10O25S•1.7HCl•9.9H2O C: 49.11%, H: 5.47%, N: 7.07%, Cl: 6.62%, F: 1.92%, S; 1.62% Found: C: 49.11%, H: 5.35%, N: 6.87%, Cl: 6.69%, F: 1.75%, S; 1.64%

bond CONH bond

CH2 [M + 1]− = 1724 Calcd. for C81H86Cl2F2N10O26•1.8HCl•9.4H2O C: 49.65%, H: 5.48%, N: 7.15%, Cl: 6.88%, F: 1.94% Found: C: 49.66%, H: 5.54%, N: 7.01%, Cl: 6.91%, F: 1.80%

TABLE 33 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemetal Analysis

bond CONH bond

CH2 [M + 3]⁺ = 1738 [M + 1]⁻ = 1736 Calcd. for C80H84Cl3N11O27•1.1HCl•10.1H2O C: 49.02%, H: 5.42%, Cl: 7.42%, N: 7.86% Found: C: 48.94%, H: 5.40%, Cl: 7.54%, N: 8.03%

bond CONH bond

CH2 [M + 1]⁻ = 1733 Calcd. for C81H87Cl2N11O28•1.6HCl•9.9H2O C: 49.38%, H: 5.55%, Cl: 6.48%, N: 7.82% Found: C: 49.31%, H: 5.55%, Cl: 6.41%, N: 8.11%

bond CONH bond

CH2 [M + 3]⁺ = 1755 [M + 1]⁻ = 1753 Calcd. for C80H84BrCl2FN10O25•2.0HCl•9.1H2O C: 48.23%, H: 5.27%, Br: 4.01%, Cl: 7.12%, F: 0.95%, N: 7.03% Found: C: 48.19%, H: 5.04%, Br: 3.82%, Cl: 7.09%, F: 1.10%, N: 7.05%

TABLE 34

bond CONH bond

CH2 [M + 3]⁺ = 1753 [M + 1]⁻ = 1751 Calcd. for C82H89Cl3N10O27•1.2HCl•9.2H2O C: 50.19%, H: 5.58%, Cl: 7.59%, N: 7.14% Found: C: 50.18%, H: 5.48%, Cl: 7.60%, N: 7.19%

bond CONH bond

CH2 [M + 3]⁺ = 1737 [M + 1]⁻ = 1735 Calcd. for C82H89Cl3N10O26•1.2HCl•8.9H2O C: 50.74%, H: 5.61%, Cl: 7.67%, N: 7.22% Found: C: 50.74%, H: 5.58%, Cl: 7.73%, N: 7.46%

bond CONH bond

CH2 [M + 3]⁺ = 1757 [M + 1]⁻ = 1755 Calcd. for C81H86Cl4N10O26•1.1HCl•8.5H2O C: 49.87%, H: 5.38%, Cl: 9.27%, N: 7.18% Found: C:49.65%, H: 5.43%, Cl: 9.48%, N: 7.48%

bond CONH bond

CH2 [M + 3]⁺ = 1797 [M + 1]⁻ = 1795 Calcd. for C82H89BrCl2N10O27•1.1HCl•8.2H2O C: 49.61%, H: 5.41%, Br: 4.02%, Cl: 5.54%, N: 7.06% Found: C: 49.58%, H: 5.33%, Br: 3.72%, Cl: 5.61%, N: 7.30%

bond CONH bond

CH2 [M + 3]⁺ = 1707 [M + 1]⁻ = 1705 Calcd. for C81H87Cl3N10O25•1.1HCl•9.8H2O C: 50.57%, H: 5.64%, Cl: 7.56%, N: 7.28% Found: C: 50.55%, H: 5.55%, Cl: 7.62%, N: 7.48%

TABLE 35

bond CONH bond

CH2 [M + 3]⁺ = 1726 [M + 1]⁻ = 1724 Calcd. for C83H88Cl2N12O25•2.2HCl•10.8H2O C: 49.86%, H: 5.64%, Cl: 7.45%, N: 8.41% Found: C: 49.82%, H: 5.48%, Cl: 7.50%, N: 8.58%

bond CONH bond

CH2 [M + 3]⁺ = 1689 [M + 1]⁻ = 1687 Calcd. for C81H88Cl2N10O26•1.3HCl•10.5H2O C: 50.54%, H: 5.78%, Cl: 6.08%, N: 7.28% Found: C: 50.47%, H: 5.73%, Cl: 6.14%, N: 7.57%

bond CONH bond

CH2 [M + 3]⁺ = 1675 [M + 1]⁻ = 1673 Calcd. for C80H86Cl2N10O26•1.1HCl•9.9H2O C: 50.76%, H: 5.69%, Cl: 5.81%, N: 7.40% Found: C: 50.82%, H: 5.60%, Cl: 5.81%, N: 7.18%

bond CONH bond

CH2 [M + 3]⁺ = 1698 [M + 1]⁻ = 1696 Calcd. for C82H87Cl2N11O25•1.4HCl•10.3H2O C: 50.92%, H: 5.68%, Cl: 6.23%, N: 7.97% Found: C: 50.92%, H: 5.53%, Cl: 6.22%, N: 8.31%

bond CONH bond

CH2 [M + 3]⁺ = 1775 [M + 1]⁻ = 1773 Calcd. for C85H95Cl2N11O27•1.3HCl•11.8H2O C: 50.20%, H: 5.94%, Cl: 5.75%, N: 7.58% Found: C: 50.21%, H: 5.79%, Cl: 5.69%, N: 7.63%

TABLE 36

bond CONH bond

CH2 [M + 3]⁺ =1761 [M + 1]⁻ =1759 Calcd. for C81H85Cl3N14O25•1.5HCl•9.6H2O C: 48.92%, H: 5.36%, Cl: 8.02%, N: 9.86% Found: C: 48.88%, H: 5.25%, Cl: 7.93%, N: 9.98%

bond CONH bond

CH2 [M + 3]⁺ =1705 [M + 1]⁻ =1703 Calcd. for C79H84Cl2N12O27•1.8HCl•10.3H2O C: 48.52%, H: 5.48%, Cl: 6.89%, N: 8.59% Found: C: 48.52%, H: 5.33%, Cl: 6.83%, N: 8.46%

bond CONH bond

CH2 [M + 3]⁺ =1725 [M + 1]⁻ =1723 Calcd. for C81H86Cl2F2N10O26•1.7HCl•10.4H2O C: 49.29%, H: 5.54%, Cl: 6.65%, F: 1.93%, N: 7.10% Found: C: 49.26%, H: 5.41%, Cl: 6.71%, F: 1.82%, N: 7.25%

bond CONH bond

CH2 [M + 3]⁺ =1735 [M + 1]⁻ =1732 Calcd. for C81H87Cl2N11O28•1.0HCl•9.3H2O C: 50.21%, H: 5.55%, Cl: 5.49%, N: 7.95% Found: C: 50.17%, H: 5.44%, Cl: 5.49%, N: 8.05%

bond CONH bond

CH2 [M + 3]⁺ =1786 [M + 1]⁻ =1787 Calcd. for C85H96Cl2N12O272•1HCl•11.1H2O C: 49.43%, H: 5.87%, Cl: 7.04%, N: 8.14% Found: C: 49.43%, H: 5.66%, Cl: 6.90%, N: 7.98%

TABLE 37

bond CONH bond

CH2 [M + 3]⁺ = 1759 [M + 1]⁻ = 1757 Calcd. for C85H94Cl2N10O27•1.8HCl•11.3H2O C: 50.35%, H: 5.89%, Cl: 6.64%, N: 6.91% Found: C: 50.33%, H: 5.76%, Cl: 6.58%, N: 7.00%

bond CONH bond

CH2 [M + 3]⁺ = 1764 [M + 1]⁻ = 1762 Calcd. for C82H89Cl2N11O29•1.9HCl•10.8H2O C: 48.58%, H: 5.59%, Cl: 6.82%, N: 7.60% Found: C: 48.50%, H: 5.49%, Cl: 6.90%, N: 7.75%

bond CONH bond

CH2 [M + 3]⁺ = 1738 [M + 1]⁻ = 1736 Calcd. for C80H84Cl3N11O27•1.6HCl•11.1H2O C: 48.13%, H: 5.44%, Cl: 8.17%, N: 7.72% Found: C: 48.12%, H: 5.40%, Cl: 8.21%, N: 7.66%

bond CONH bond

CH2 [M + 1]⁻ = 1693 Calcd. for C79H84Cl3N11O25•1.6HCl•10.7H2O C: 48.78%, H: 5.54%, Cl: 8.38%, N: 7.92% Found: C: 48.71%, H: 5.41%, Cl: 8.54%, N: 8.08%

bond CONH bond

CH2 [M + 3]⁺ = 1789 Calcd. for C88H88Cl2N10O27•1.6HC•11.8H2O C: 51.32%, H: 5.54%, Cl: 6.20%, N: 6.80% Found: C: 51.27%, H: 5.40%, Cl: 6.33%, N: 6.95%

TABLE 38

bond CONH bond

CH2 [M + 1]⁻ = 1714 Calcd. for C82H89Cl2N11O26•1.8HCl•10.7H2O C: 49.89%, H: 5.73%, Cl: 6.82%, N: 7.81% Found: C: 49.87%, H: 5.61%, Cl: 6.83%, N: 7.95%

bond CONH bond

CH2 [M + 3]⁺ = 1707 [M + 1]⁻ = 1705 Calcd. for C81H87Cl2FN10O26•1.2HCl•9.9H2O C: 50.44%, H: 5.64%, Cl: 5.88%, F: 0.99%, N: 7.26% Found: C: 50.44%, H: 5.56%, Cl: 5.95%, F: 0.98%, N: 7.30%

bond CONH bond

CH2 [M + 1]⁻ = 1672 Calcd. for C80H87Cl2N11O25•1.3HCl•10.6H2O C: 50.26%, H: 5.77%, Cl: 6.12%, N: 8.06% Found: C: 50.17%, H: 5.76%, Cl: 6.24%, N: 8.24%

bond CONH bond

CH2 [M + 1]⁻ = 1823 Calcd. for C87H88Cl2N10O28S•1.7HCl•9.9H2O C: 50.60%, H: 5.34%, Cl: 6.35%, N: 6.78%, S: 1.55% Found: C: 50.67%, H: 5.26%, Cl: 6.19%, N: 6.59%, S: 1.55%

bond CONH bond

CH2 [M + 3]⁺ = 1742 Calcd. for C81H86Cl2F3N11O25•1.7HCl•10.0H2O C: 49.04%, H: 5.47%, Cl: 6.61%, F: 2.87%, N: 7.77% Found: C: 48.99%, H: 5.34%, Cl: 6.51%, F: 2.78%, N: 7.89%

TABLE 39

bond CONH bond

CH2 [M + 3]⁺ = 1701 [M + 1]⁻ = 1699 Calcd. for C82H88Cl2N10O26•1.5HCl•10.2H2O C: 50.79%, H: 5.71%, Cl: 6.40%, N: 7.22% Found: C: 50.73%, H: 5.61%, Cl: 6.45%, N: 7.49%

bond CONH bond

CH2 [M + 3]⁺ = 1729 [M + 1]⁻ = 1727 Calcd. for C80H83Cl3F2N10O25•1.5HCl•9.5H2O C: 49.15%, H: 5.34%, Cl: 8.16%, F: 1.94%, N: 7.17% Found: C: 49.05%, H: 5.27%, Cl: 8.28%, F: 1.81%, N: 7.36%

bond CONH bond

CH2 [M + 1]⁻ = 1777 Calcd. for C81H83Cl3F4N10O25•1.7HCl•10.6H2O C: 47.88%, H: 5.25%, Cl: 8.20%, F: 3.74%, N: 6.89% Found: C: 47.92%, H: 5.17%, Cl: 8.13%, F: 3.35%, N: 6.86%

bond CONH bond

CH2 [M + 3]⁺ = 1757 Calcd. for C82H87Cl2F3N10O26•1.7HCl•8.4H2O C: 50.00%, H: 5.40%, Cl: 6.66%, F: 2.89%, N: 7.11% Found: C: 49.91%, H: 5.34%, Cl: 6.84%, F: 2.75%, N: 7.36%

bond CONH bond

CH2 [M + 1]⁻ = 1710 Calcd. for C80H84Cl3FN10O25•1.4HCl•9.9H2O C: 49.52%, H: 5.46%, Cl: 8.04%, F: 0.98%, N: 7.22% Found: C: 49.34%, H: 5.38%, Cl: 8.04%, F: 0.96%, N: 7.52%

TABLE 40

bond CONH bond

CH2 [M + 3]⁺ = 1701 [M + 1]⁻ = 1699 Calcd. for C83H92Cl2N10O25•1.8HCl•9.8H2O C: 51.31%, H: 5.88%, Cl: 6.93%, N: 7.21% Found: C: 51.24%, H: 5.77%, Cl: 6.88%, N: 7.39%

bond CONH bond

CH2 [M + 3]⁺ = 1719 [M + 1]⁻ = 1717 Calcd. for C82H90Cl2N10O27•1.6HCl•10.0H2O C: 50.32%, H: 5.75%, Cl: 6.52%, N: 7.16% Found: C: 50.32%, H: 5.73%, Cl: 6.52%, N: 7.20%

bond CONH bond

CH2 [M + 3]⁺ = 1691 Calcd. for C81H87Cl2FN10O25•1.9HCl•9.9H2O C: 50.20%, H: 5.65%, Cl: 7.13%, F: 0.98%, N: 7.23% Found: C: 50.17%, H: 5.55%, Cl: 7.13%, F: 0.90%, N: 7.48%

bond CONH bond

CH2 [M + 3]⁺ = 1739 [M + 1]⁻ = 1737 Calcd. for C81H84Cl2F2N10O27•1.6HCl•9.5H2O C: 49.44%, H: 5.36%, Cl: 6.49%, F: 1.93%, N: 7.12% Found: C: 49.37%, H: 5.33%, Cl: 6.53%, F: 1.88%, N: 7.32%

bond CONH bond

CH2 [M + 3]⁺ = 1719 [M + 1]⁻ = 1717 Calcd. for C82H90Cl2N10O27•1.6HCl•9.5H2O C: 50.56%, H: 5.72%, Cl: 6.55%, N: 7.19% Found: C: 50.52%, H: 5.60%, Cl: 6.59%, N: 7.27%

TABLE 41

bond CONH bond

CH2 [M + 1]⁻ =1813 Calcd. for C86H91Cl2N11O27S•1.8HCl•9.0H2O C: 50.60%, H: 5.47%, Cl: 6.60%, N: 7.55%, S: 1.57% Found: C: 50.57%, H: 5.33%, Cl: 6.63%, N: 7.51%, S: 1.40%

bond CONH bond

CH2 [M + 3]⁺ =1735 [M + 1]⁻ =1733 Calcd. for C86H90Cl2N10O25•1.9HCl•8.3H2O C: 52.88%, H: 5.60%, Cl: 7.08%, N: 7.17% Found: C: 52.83%, H: 5.47%, Cl: 7.11%, N: 7.39%

bond CONH bond

CH2 [M + 1]⁻ =1716 Calcd. for C83H92Cl2N10O26•1.8HCl•9.1H2O C: 51.22%, H: 5.80%, Cl: 6.92%, N: 7.20% Found: C: 51.18%, H: 5.72%, Cl: 6.83%, N: 7.47%

bond CONH bond

CH2 [M + 3]⁺ =1649 [M + 1]⁻ =1647 Calcd. for C77H84Cl2N12O25•1.8HCl•9.6H2O C: 49.01%, H: 5.61%, Cl: 7.14%, N: 8.91% Found: C: 49.00%, H: 5.52%, Cl: 7.13%, N: 9.00%

bond CONH bond

CH2 [M + 3]⁺ =1778 [M + 1]⁻ =1776 Calcd. for C83H85Cl4N11O25•2.1HCl•10.2H2O C: 48.90%, H: 5.31%, Cl: 10.61%, N: 7.56% Found: C: 48.92%, H: 5.26%, Cl: 10.60%, N: 7.68%

TABLE 42

bond CONH bond

CH2 [M + 1]⁻ = 1674 Calcd. for C79H85Cl2N11O26•2.5HCl•10.0H2O C: 48.74%, H: 5.57%, Cl: 8.19%, N: 7.91% Found: C: 48.73%, H: 5.55%, Cl: 8.16%, N: 8.04%

bond CONH bond

CH2 [M + 1]⁻ = 1755 Calcd. for C83H88Cl2N12O27•2.0HCl•10.3H2O C: 49.47%, H: 5.53%, Cl: 7.04%, N: 8.34% Found: C: 49.40%, H: 5.50%, Cl: 7.02%, N: 8.61%

bond CONH bond

CH2 [M + 1]⁻ = 1774 Calcd. for C87H89Cl2N11O26•2.6HCl•10.4H2O C: 50.78%, H: 5.51%, Cl: 7.93%, N: 7.49% Found: C: 50.76%, H: 5.59%, Cl: 7.87%, N: 7.70%

bond CONH bond

CH2 [M + 1]⁻ = 1750 Calcd. for C81H89Cl2N11O27S•2.0HCl•9.4H2O C: 48.79%, H: 5.55%, Cl: 7.11%, N: 7.73%, S: 1.16% Found: C: 48.72%, H: 5.50%, Cl: 7.22%, N: 7.95%, S: 1.77%

bond CONH bond

CH2 [M + 1]⁻ = 1822 Calcd. for C85H94Cl2FN11O27S•1.9HCl•10.1H2O C: 49.20%, H: 5.64%, Cl: 6.66%, F: 0.92%, N: 7.43%, S: 1.55% Found: C: 49.16%, H: 5.57%, Cl: 6.58%, F: 0.84%, N: 7.59%, S: 1.62%

TABLE 43

bond CONH bond

CH2 [M + 3]⁺ = 1758 [M + 1]⁻ = 1756 Calcd. for C85H95Cl2N11O28•1.7HCl•8.7H2O C: 51.66%, H: 5.82%, Cl: 6.64%, N: 7.80% Found: C: 51.64%, H: 5.83%, Cl: 6.63%, N: 7.88%

bond CONH bond

CH2 [M + 1]⁻ = 1819 Calcd. for C86H97Cl2N11O27S•2.0HCl•8.5H2O C: 50.49%, H: 5.72%, Cl: 6.93%, N: 7.53%, S: 1.57% Found: C: 50.45%, H: 5.69%, Cl: 6.91%, N: 7.75%, S: 1.56%

bond CONH bond

CH2 [M + 1]⁻ = 1781 Calcd. for C83H89Cl2F3N12O25•2.4HCl•10.3H2O C: 48.50%, H: 5.49%, Cl: 7.59%, F: 2.77%, N: 8.18% Found: C: 48.48%, H: 5.36%, Cl: 7.53%, F: 2.51%, N: 8.37%

TABLE 44 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemetal Analysis

bond CONH bond

CH2 1823 [M + H]+ Calcd. for C87H92Cl2N12O28 3.2(HCl) 14(H2O) C: 47.64% H: 5.66% Cl: 8.40% N: 7.66% O: 30.63% Found: H (%) 5.23 C (%) 47.59 N (%) 7.74 Cl (%) 8.40

bond CONH bond

CH2 1823 [M + H]+ Calcd. For C87H92Cl2N12O28 2.9(HCl) 8(H2O) C: 50.37% H: 5.39% Cl: 8.37% N: 8.10% O: 27.76% Found: H (%) 5.24 C (%) 50.23 N (%) 8.22 Cl (%) 8.12

bond CONH bond

CH2 1830 [M + H]+ Calcd. For C87H97Cl2N11O29 2(HCl) 11(H2O) C: 49.69% H: 5.80% Cl: 6.74% N: 7.33% O: 30.44% Found: Cl (%) 6.85 H (%) 5.62 C (%) 49.57 N (%) 7.34

TABLE 45

bond CONH bond

CH2 1818 [M + H]+ Calcd. For C85H93Cl2N11O30 2(HCl) 10(H2O) C: 49.26% H: 5.59% Cl: 6.84% N: 7.43% O: 30.88% Found: Cl (%) 6.81 H (%) 5.14 C (%) 49.06 N (%) 7.57

bond CONH bond

CH2 1786 [M + H]+ Calcd. For C85H93Cl2N11O28 2(HCl) 11(H2O) C: 49.59% H: 5.73% Cl: 6.89% N: 7.48% O: 30.31% Found: Cl (%) 7.06 H (%) 5.26 C (%) 49.60 N (%) 7.68

bond CONH bond

CH2 1828 [M + H]+ Calcd. For C88H99Cl2N11O28 2(HCl) 11(H2O) C: 50.31% H: 5.90% Cl: 6.75% N: 7.33% O: 29.70% Found: Cl (%) 6.67 H (%) 5.67 C (%) 50.13 N (%) 7.24

bond CONH bond

CH2 1732 [M + H]+ Calcd. For C81H87Cl2N11O28 2(HCl) 11(H2O) C: 48.53% H: 5.58% Cl: 7.07% N: 7.69% O: 31.13% Found: Cl (%) 7.28 H (%) 5.31 C (%) 48.31 N (%) 7.72

bond CONH bond

CH2 1808 [M + H]+ Calcd. For C87H91Cl2N11O28 2(HCl) 15(H2O) C: 48.54% H: 5.76% Cl: 6.59% N: 7.16% O: 31.96% Found: Cl (%) 6.63 H (%) 5.08 C (%) 48.62 N (%) 7.28

bond CONH bond

CH2 1822 [M + H]+ Calcd. For C88H93Cl2N11O28 2(HCl) 15(H2O) C: 48.78% H: 5.81% Cl: 6.54% N: 7.11% O: 31.75% Found: Cl (%) 6.49 H (%) 5.38 C (%) 48.22 N (%) 7.84

TABLE 46

bond CONH bond

CH2 1814 [M + H]+ Calcd. For C87H97Cl2N11O28 1.2(HCl) 12(H2O) C: 50.34% H: 5.93% Cl: 5.47% N: 7.42% O: 30.83% Found: Cl (%) 5.76 H (%) 5.71 C (%) 50.43 N (%) 7.57

TABLE 47 R^(A) R^(B) R^(C) R^(D)

OH or NRR′ H or CH₂—NRR′ H R^(B) R^(C) R^(D) Mass Elemetal Analysis

H H [M + 1]⁻ = 1810 Calcd. for C85H96Cl4N12O24•3.0HCl•12.4H2O C: 47.61%, H: 5.82%, N: 7.84%, Cl: 11.57% Found: C: 47.58%, H: 5.62%, N: 7.97%, Cl: 11.5%

H H [M + 3]⁺ = 1784 [M + 1]⁻ = 1782 Calcd. for C82H87Cl4N11O26•2.0HCl•10.8H2O C: 48.00%, H: 5.43%, N: 7.51%, Cl: 10.37% Found: C: 48.00%, H: 5.24%, N: 7.47%, Cl: 10.30%

H H [M + 3]⁺ = 1797 [M + 1]⁻ = 1799 Calcd. for C83H89Cl4N11O26•2.0HCl•10.2H2O C: 48.51%, H: 5.46%, N: 7.50%, Cl: 10.35% Found: C: 48.47%, H: 5.33%, N: 7.44%, Cl: 10.41%

H H [M + 1]⁻ = 1888 Calcd. for C86H95Cl4N11O29•1.8HCl•12.3H2O C: 47.47%, H: 5.62%, N: 7.08%, Cl: 9.45% Found: C: 47.46%, H: 5.44%, N: 7.06%, Cl: 9.52%

TABLE 48

H H [M + 1]⁻ =1903 Calcd. for C87H99Cl4N11O29•2.1HCl•10.2H2O C: 48.27%, H: 5.66%, N: 7.12%, Cl: 9.99% Found: C: 48.26%, H: 5.63%, N: 7.25%, Cl: 9.99%

H H [M + 3]⁺ =1809 [M + 1]⁻ =1807 Calcd. for C83H87Cl4N13O25•2.7HCl•12.5H2O C: 46.76%, H: 5.42%, N: 8.54%, Cl: 11.14% Found: C: 46.78%, H: 5.19%, N: 8.56%, Cl: 11.10% OH

H [M + 1]⁻ =1842 Calcd. for C85H95Cl4N11O27•2.6HCl•11.2H2O C: 47.68%, H: 5.85%, N: 7.20%, Cl: 10.93% Found: C: 47.64%, H: 5.45%, N: 7.41%, Cl: 10.97% OH

H [M + 1]⁻ =1933 Calcd. for C88H101Cl4N11O30•2.8HCl•10.9H2O C: 47.33%, H: 5.67%, N: 6.90%, Cl: 10.80% Found: C: 47.29%, H: 5.53%, N: 7.00%, Cl: 10.83% OH

H [M + 1]⁻ =1869 Calcd. for C86H97Cl4N13O26•3.7HCl•11.2H2O C: 46.80%, H: 5.62%, N: 8.25%, Cl: 12.37% Found: C: 46.75%, H: 5.61%, N: 8.42%, Cl: 12.38% OH

H [M + 1]⁻ =1849 Calcd. for C82H90Cl4N11O28P•2.0HCl•11.0H2O C: 46.42%, H: 5.42%, N: 7.26%, Cl: 10.03%, P: 1.46% Found: C: 46.42%, H: 5.42%, N: 7.21%, Cl: 10.03%, P: 1.82% OH

H [M + 3]⁺ =1872 [M + 1]⁻ =1870 Calcd. for C85H92Cl4N12O28•2.8HCl•11.2H2O C: 46.93%, H: 5.43%, N: 7.73%, Cl: 11.08% Found: C: 46.89%, H: 5.39%, N: 7.77%, Cl: 11.15% OH

H [M + 3]⁺ =1919 [M + 1]⁻ =1917 Calcd. for C87H97Cl4N11O30.3•2HCl•12.1H2O C: 46.37%, H: 5.56%, N: 6.84%, Cl: 11.33% Found: C: 46.36% H: 5.34%, N: 7.00%, Cl: 11.29%

TABLE 49 OH

H [M + 1]⁻ = 1849 Calcd. for C86H93Cl4N13O25•3.7HCl•12.2H2O C: 46.84%, H: 5.54%, N: 8.26%, Cl: 12.38% Found: C: 46.83%, H: 5.52%, N: 8.34%, Cl: 12.41% OH

H [M + 1]⁻ = 1912 Calcd. for C87H98Cl4N14O27•2.8HCl•12.4H2O C: 46.67%, H: 5.65%, N: 8.76%, Cl: 10.77% Found: C: 46.69%, H: 5.60%, N: 8.75%, Cl: 10.72% OH

H [M + 1]⁻ = 1893 Calcd. for C87H93Cl4N13O27•3.6HCl•12.5H2O C: 46.42%, H: 5.44%, N: 8.09%, Cl: 11.97% Found: C: 46.39%, H: 5.27%, N: 8.11%, Cl: 11.95% OH

H [M + 1]⁻ = 1798 Calcd. for C83H92Cl4N12O25•3.4HCl•13.2H2O C: 46.13%, H: 5.68%, N: 7.78%, Cl: 12.14% Found: C: 46.11%, H: 5.50%, N: 7.94%, Cl: 12.17%

H H [M + 3]⁺ = 1814 [M + 1]⁻ = 1812 Calcd. for C84H93Cl4N11O26•1.6HCl•9.4H2O C: 49.40%, H: 5.60%, Cl: 9.72%, N: 7.54% Found: C: 49.41%, H: 5.76%, Cl: 9.78%, N: 7.30%

H H [M + 3]⁺ = 1812 [M + 1]⁻ = 1810 Calcd. for C85H97Cl5N12O24•1.2HCl•10.4H2O C: 49.10%, H: 5.77%, Cl: 10.57%, N: 8.08% Found: C: 49.18%, H: 5.76%, Cl: 10.62%, N: 7.53%

H H [M + 3]⁺ = 1841 [M + 1]⁻ = 1839 Calcd. for C85H95Cl4N13O25•2.3HCl•9.6H2O C: 48.68%, H: 5.60%, Cl: 10.65%, N: 8.68% Found: C: 48.83%, H: 5.63%, Cl: 10.60%, N: 8.23% OH

H [M + 3]⁺ = 1829 [M + 1]⁻ = 1827 Calcd. for C84H81Cl4N11O27•1.4HCl•8.7H2O C: 49.55%, H: 5.44%, Cl: 9.40%, N: 7.57% Found: C: 49.60%, H: 5.51%, Cl: 9.34%, N: 7.57%

TABLE 50 OH

H [M + 3]⁺ =1864 [M + 1]⁻ =1862 Calcd. for C83H91Cl4N11O28S•1.5HCl•11.2H2O C: 47.00%, H: 5.46%, Cl: 9.19%, N: 7.26%, S: 1.51% Found: C: 47.10%, H: 5.30%, Cl: 9.11%, N: 6.99%, S: 1.42% OH

H [M + 3]⁺ =1896 [M + 1]⁻ =1894 Calcd. for C88H100Cl4N14O25•2.9HCl•10.2H2O C: 48.37%, H: 5.69%, Cl: 11.20%, N: 8.97% Found: C: 48.39%, H: 5.72%, Cl: 11.15%, N: 8.95%

H H [M + 3]⁺ =1842 [M + 1]⁻ =1840 Calcd. for C84H89Cl4N11O28•1.1HCl•7.6H2O C: 49.96%, H: 5.26%, Cl: 8.95%, N: 7.63% Found: C: 50.09%, H: 5.25%, Cl: 8.90%, N: 6.89%

H H [M + 3]⁺ =1834 [M + 1]⁻ =1832 Calcd. for C82H89Cl4N11O27S•0.6HCl•5.7H2O C: 50.27%, H: 5.20%, Cl: 8.32%, N: 7.86%, S: 1.64% Found: C: 50.46%, H: 5.36%, Cl: 8.25%, N: 6.91%, S: 1.47%

H H [M + 3]⁺ =1866 [M + 1]⁻ =1864 Calcd. for C87H98Cl4N14O24•2.1HCl•8.6H2O C: 49.83%, H: 5.64%, Cl: 10.31%, N: 9.35% Found: C: 50.09%, H: 5.64%, Cl: 10.24%, N: 8.33%

H H [M + 3]⁺ =1883 [M + 1]⁻ =1881 Calcd. for C86H96Cl4N14O26•2.5HCl•9.2H2O C: 48.26%, H: 5.50%, Cl: 10.77%, N: 9.16% Found: C: 48.41%, H: 5.46%, Cl: 10.68%, N: 8.60%

H H [M + 3]⁺ =1812 [M + 1]⁻ =1810 Calcd. for C84H95Cl4N13O24•3.2HCl•9.7H2O C: 47.95%, H: 5.63%, Cl: 12.13%, N: 8.65% Found: C: 48.03%, H: 5.56%, Cl: 11.91%, N: 8.39%

H H [M + 3]⁺ =1813 [M + 1]⁻ =1811 Calcd. for C84H94Cl4N12O25•2.6HCl•9.5H2O C: 48.52%, H: 5.60%, Cl: 11.25%, N: 8.08% Found: C: 48.48%, H: 5.52%, Cl: 11.27%, N: 8.00%

TABLE 51 OH

H [M + 3]⁺ = 1842 [M + 1]⁻ = 1840 Calcd. for C86H99Cl4N12O25•4HCl•10H2O C: 56.06%, H: 5.42%, N: 9.12%, Cl: 7.70% Found: C: 46.85%, H: 5.58%, N: 7.84%, Cl: 12.74% OH

H [M + 3]⁺ = 1885 [M + 1]⁻ = 1883 Calcd. for C87H98Cl4N12O27•4HCl•10H2O C: 55.42%, H: 5.24%, N: 8.91%, Cl: 7.52% Found: C: 47.10%, H: 5.51%, N: 7.75%, Cl: 12.81% OH

H [M + 3]⁺ = 1814 [M + 1]⁻ = 1812 Calcd. for C83H89Cl4N11O27•3HCl•12H2O C: 54.94%, H: 4.94%, N: 8.49%, Cl: 7.82% Found: C: 46.74%, H: 5.30%, N: 7.42%, Cl: 11.41%

TABLE 52 R^(A) R^(B) R^(C) R^(D)

OH or NRR′ H or CH₂—NRR′ H R^(B) R^(C) R^(D) Mass Elemetal Analysis —N[(CH₂)₂OH]₂ H H [M + 3]⁺ = 1858 Calcd. for C87H99Cl2F3N12O26•3.7HCl•11.4H2O [M + 1]⁻ = 1856 C: 47.56%, H: 5.76%, N: 7.65%, Cl: 9.20%, F: 2.59% Found: C: 47.72%, H: 5.59%, N: 7.88%, Cl: 9.25%, F: 2.29% —NH(CH₂)₃NMe₂ H H [M + 3]⁺ = 1855 Calcd. for C88H102Cl2F3N13O24•3.6HCl•10.5H2O [M + 1]⁻ = 1853 C: 48.61%, H: 5.87%, N: 8.38%, Cl: 9.13%, F: 2.62% Found: C: 48.55%, H: 5.75%, N: 8.52%, Cl: 9.16%, F: 2.47% —NH(CH₂)₂N⁺Me₃ H H [M + 3]⁺ = 1855 Calcd. for C88H103Cl3F3N13O24•2.7HCl•12.3H2O [M + 1]⁻ = 1853 C: 47.82%, H: 5.94%, N: 8.24%, Cl: 9.14%, F: 2.58% Found: C: 47.82%, H: 5.85%, N: 8.34%, Cl: 9.11%, F: 2.47% —NHCH₂CO₂H H H [M + 1]⁻ = 1825 Calcd. for C85H93Cl2F3N12O26•2.6HCl•11.7H2O C: 47.88%, H: 5.63%, N: 7.88%, Cl: 7.65%, F: 2.67% Found: C: 47.91%, H: 5.64%, N: 7.97%, Cl: 7.69%, F: 2.52% —NH(CH₂)₂CO₂H H H [M + 3]⁺ = 1842 Calcd. for C86H95Cl2F3N12O26•2.0HCl•8.9H2O [M + 1]⁻ = 1840 C: 49.81%, H: 5.58%, N: 8.10%, Cl: 6.84%, F: 2.75% Found: C: 49.78%, H: 5.58%, N: 8.29%, Cl: 6.90%, F: 2.57%

TABLE 53

H H [M + 3]⁺ = 1884 [M + 1]⁻ = 1882 Calcd. for C88H101Cl2F3N14O25•3.6HCl•11.1H2O C: 47.74%, H: 5.77%, N: 8.86%, Cl: 8.97%, F: 2.57% Found: C: 47.70%, H: 5.73%, N: 8.99%, Cl: 8.93%, F: 2.45%

H H [M + 1]⁻ = 1929 Calcd. for C89H101Cl2F3N12O29•2.5HCl•10.7H2O C: 48.27%, H: 5.68%, N: 7.59%, Cl: 7.20%, F: 2.57% Found: C: 48.21%, H: 5.63%, N: 7.74%, Cl: 7.21%, F: 2.46%

H H [M + 1]⁻ = 1945 Calcd. for C90H105Cl2F3N12O29•2.9HC.10.9H2O C: 48.14%, H: 5.80%, N: 7.49%, Cl: 7.74%, F: 2.54% Found: C: 48.03%, H: 5.79%, N: 7.83%, Cl: 7.68%, F: 2.32%

H H [M + 1]⁻ = 1884 Calcd. for C87H95Cl2F3N12O28•2.8HCl•10.8H2O C: 47.90%, H: 5.52%, N: 7.71%, Cl: 7.80%, F: 2.61% Found: C: 47.87%, H: 5.39%, N: 7.77%, Cl: 7.82%, F: 2.50%

H H [M + 3]⁺ = 1899 [M + 1]⁻ = 1897 Calcd. for C89H102Cl2F3N13O26•3.5HCl•12.1H2O C: 47.65%, H: 5.83%, N: 8.12%, Cl: 8.69%, F: 2.54% Found: C: 47.62%, H: 5.67%, N: 8.24%, Cl: 8.61%, F: 2.34% OH

H [M + 3]⁺ = 1871 [M + 1]⁻ = 1869 Calcd. for C87H97Cl2F3N12O27•3.5HCl•12.5H2O C: 55.86%, H: 5.23%, N: 8.99%, Cl: 3.79%, F: 3.05% Found: C: 46.95%, H: 5.53%, N: 7.70%, Cl: 8.71%, F: 2.34% OH

H [M + 1]⁻ = 1885 Calcd. for C88H101Cl2F3N12O27•13HCl•3H2O C: 56.02%, H: 5.40%, N: 8.91%, Cl: 3.76%, F: 3.02% Found: C: 47.50%, H: 5.72%, N: 7.74%, Cl: 8.10%, F: 2.38% OH

H [M + 3]⁺ = 1907 [M + 1]⁻ = 1905 Calcd. for C86H97Cl2F3N12O28S•2HCl•11H2O C: 54.17%, H: 5.13%, N: 8.82%, Cl: 3.72%, F: 2.99%, S: 1.69% Found: C: 47.61%, H: 5.52%, N: 7.82%, Cl: 6.47%, F: 2.52%, S: 1.26% OH

H [M + 3]⁺ = 1893 [M + 1]⁻ = 1891 Calcd. for C85H96Cl2F3N12O28P•2.5HCl•11H2O C: 53.94%, H: 5.11%, N: 8.88%, Cl: 3.75%, F: 3.01% Found: C: 46.84%, H: 5.54%, N: 7.73%, Cl: 7.24%, F: 2.48%

TABLE 54 OH

H [M + 3]⁺ =1913 [M + 1]⁻ =1911 Calcd. for C89H103Cl2F3N14O26•3HCl•12H2O C: 55.89%, H: 5.43%, N: 10.25%, Cl: 3.71%, F: 2.98% Found: C: 47.52%, H: 5.81%, N: 9.21%, Cl: 8.16%, F: 2.29% OH

H [M + 3]⁺ =1938 [M + 1]⁻ =1936 Calcd. for C91H106Cl2F3N15O25•3.5HCl•11H2O C: 56.40%, H: 5.51%, N: 10.84%, Cl: 3.66%, F: 2.94% Found: C: 48.07%, H: 5.93%, N: 9.67%, Cl: 8.48%, F: 2.27% OH

H [M + 3]⁺ =1977 [M + 1]⁻ =1975 Calcd. for C91H107Cl2F3N12O30•3HCl•12H2O C: 55.29%, H: 5.46%, N: 8.50%, Cl: 3.59%, F: 2.88% Found: C: 47.42%, H: 5.89%, N: 7.42%, Cl: 7.42%, F: 2.36% OH

H [M + 3]⁺ =1914 [M + 1]⁻ =1912 Calcd. for C88H98Cl2F3N13O28•3HCl•13H2O C: 55.23%, H: 5.16%, N: 9.51%, Cl: 3.71%, F: 2.98% Found: C: 46.77%, H: 5.47%, N: 8.16%, Cl: 7.95%, F: 2.43%

H H [M + 3]⁺ =1877 [M + 1]⁻ =1875 Calcd. for C85H95Cl2F3N12O27S•2HCl•10H2O C: 54.40%, H: 5.10%, N: 8.96%, Cl: 3.78%, F: 3.04%, S: 1.71% Found: C: 48.06%, H: 5.37%, N: 8.11%, Cl: 6.77%, F: 2.58%, S: 1.35%

Example 12

The following compounds were prepared in a similar manner as described above. TABLE 55 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 3]⁺ =1820 [M + 1]⁻ =1818 calcd. for C88H93Cl2N13O26•1.8HCl•10.6H2O C: 50.91%, H: 5.63%, N: 8.77%, Cl: 6.49% found: C: 50.91%, H: 5.55%, N: 8.77%, Cl: 6.50%

bond CONH bond

CH2 [M + 1]⁻ =1797 calcd. for C87H94Cl2N10O26S•1.7HCl•9.8H2O C: 51.29%, H: 5.70%, N: 6.88%, Cl: 6.44%, S: 1.57% found: C: 51.26%, H: 5.67%, N: 6.93%, Cl: 6.39%, S: 1.38%

bond CONH bond

CH2CH2 [M + 3]⁺ =1750 calcd. for C80H90Cl2F3N11O26•1.9HCl•11.2H2O C: 47.55%, H: 5.70%, N: 7.63%, Cl: 6.84%, F: 2.82 found: C: 47.46%, H: 5.60%, N: 7.80%, Cl: 6.84%, F: 2.45

TABLE 56

bond CONH bond

CH2CH2 [M + 1]⁻ =1773 calcd. for C80H85Cl2F3N12O27•2.1HCl•13.5H2O C: 45.88%, H: 5.49%, N: 8.03%, Cl: 6.94%, F: 2.72 found: C: 45.85%, H: 5.30%, N: 8.03%, Cl: 6.92%, F: 2.96

bond CONH bond

CH2CH2 [M + 1]⁻ =1773 calcd. for C80H85Cl2F3N12O27•2.1HCl•4.3H2O C: 45.57%, H: 5.53%, N: 7.97%, Cl: 6.89%, F: 2.70 found: C: 45.52%, H: 5.28%, N: 7.98%, Cl: 6.85%, F: 2.56

bond CONH bond

CH2CH2 [M + 1]⁻ =1759 calcd. for C79H84Cl4N12O26•2.1HCl•14.2H2O C: 45.36%, H: 5.52%, N: 8.04%, Cl: 10.34% found: C: 45.23%, H: 5.46%, N: 8.34%, Cl: 10.29%

bond CONH bond

CH2CH2 [M + 3]⁺ =1803 calcd. for C82H90Cl2F3N13O26•3.0HCl•12.0H2O C: 46.30%, H: 5.54%, N: 8.56%, Cl: 8.33%, F: 2.68 found: C: 46.25%, H: 5.54%, N: 8.71%, Cl: 8.25%, F: 2.89

bond CONH bond

CH2CH2 [M + 3]⁺ =1792 calcd. for C80H85Cl2F3N12O26S•1.4HCl•12.6H2O C: 46.45%, H: 5.44%, N: 8.13%, Cl: 5.83%, S: 1.55%, F: 2.76% found: C: 46.44%, H: 5.36%, N: 8.16%, Cl: 5.81%, S: 1.58%, F: 2.88%

bond CONH bond

CH2CH2 [M + 3]⁺ =1764 calcd. for C83H94Cl2N12O27•1.2HCl•11.8H2O C: 49.38%, H: 5.93%, N: 8.33%, Cl: 5.62% found: C: 49.35%, H: 5.85%, N: 8.47%, Cl: 5.58%

TABLE 57

bond CONH bond

CH2CH2 [M + 3]⁺ =1808 calcd. for C81H86Cl2F4N12O27•1.7HCl•11.2H2O C: 46.99, H: 5.36%, N: 8.12%, Cl: 6.34%, F: 3.67 found: C: 46.97%, H: 5.30%, N: 8.23%, Cl: 6.36%, F: 3.70

bond CONH bond

CH2CH2 [M + 3]⁺ =1720 calcd. for C81H90Cl2N12O26•1.1HCl•11.0H2O C: 49.72. H: 5.83%, N: 8.59%, Cl: 5.62% found: C: 49.69%, H: 5.72%, N: 8.65%, Cl: 5.61%

bond CONH bond

CH2CH2 [M + 1]⁻ =1793 calcd. for C80H84Cl2F4N12O27•2.0HCl•13.8H2O C: 45.45, H: 5.42%, N: 7.95%, Cl: 6.71%, F: 3.59 found: C: 45.46%, H: 5.39%, N: 8.10%, Cl: 6.75%, F: 3.06

bond CONH bond

CH2CH2 [M + 3]⁺ =1790 calcd. for C81H87Cl2F3N12O27•2.1HCl•11.0H2O C: 47.15, H: 5.43%, N: 8.15%, Cl: 7.05%, F: 2.76 found: C: 47.14%, H: 5.44%, N: 8.27%, Cl: 7.09%, F: 2.75

bond CONH bond

CH2CH2CH2 [M + 3]⁺ =1794 calcd. for C81H91Cl2F3N12O27•1.8HCl•14.3H2O C: 45.98, H: 5.78%, N: 7.94%, Cl: 6.37%, F: 2.69 found: C: 45.97%, H: 5.88%, N: 7.81%, Cl: 6.45%, F: 2.35

bond CONH bond

CH2CH2CH2 [M + 3]⁺ =1790 calcd. for C81H87Cl2F3N12O27•2.2HCl•13.4H2O C: 46.10, H: 5.54%, N: 7.97%, Cl: 7.06%, F: 2.70 found: C: 46.07%, H: 5.50%, N: 7.99%, Cl: 7.13%, F: 2.54

TABLE 58

CH2 CONH bond

CH2CH2 [M + 3]⁺ = 1774 calcd. for C80H86Cl4N12O26•1.5HCl•11.7H2O C: 47.13, H: 5.48%, N: 8.24%, Cl: 9.56% found: C: 47.12%, H: 5.39%, N: 8.39%, Cl: 9.51%

CH2 CONH bond

CH2CH2 [M + 3]⁺ = 1790 calcd. for C81H87Cl2F3N12O27•1.8HCl•11.0H2O C: 47.40, H: 5.44%, N: 8.19%, Cl: 6.56%, F: 2.78 found: C: 47.32%, H: 5.34%, N: 8.40%, Cl: 6.54%, F: 2.79

TABLE 59 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 3]⁺ =1789 [M + 1]⁻ =1787 calcd. for C87H100Cl2N10O27•1.7HCl•13.2H2O C: 50.03%, H: 6.18%, N: 6.71%, Cl: 6.28% found: C: 49.98%, H: 6.06%, N: 6.80%, Cl: 6.21%

bond CONH bond

CH2 [M + 1]⁻ =1802 calcd. for C89H93Cl2N11O26•1.9HCl•13.0H2O C: 50.73%, H: 5.78%, N: 7.31%, Cl: 6.56% found: C: 50.67%, H: 5.55%, N: 7.38%, Cl: 6.52%

TABLE 60

bond NHCO NH

CH2 [M + 1]⁻ = 1784 calcd. for C83H91Cl2F3N12O25•2.3HCl•16.4H2O C: 46.07%, H: 5.87%, N: 7.77%, Cl: 7.05%, F: 2.63% found: C: 46.02%, H: 5.73%, N: 7.79%, Cl: 7.13%, F: 2.60%

bond NHCO NH

CH2 [M + 1]⁻ = 1757 calcd. for C81H86Cl2F3N11O26•1.8HCl•11.5H2O C: 47.92%, H: 5.50%, N: 7.59%, Cl: 6.64%, F: 2.81% found: C: 47.92%, H: 5.58%, N: 7.64%, Cl: 6.57%, F: 2.80%

bond NHCO NH

CH2 [M + 1]⁻ = 1757 calcd. for C81H86Cl2F3N11O26•2.0HCl•13.5H2O C: 46.92%, H: 5.59%, N: 7.43%, Cl: 6.84%, F: 2.75% found: C: 46.94%, H: 5.64%, N: 7.43%, Cl: 6.87%, F: 2.76%

bond CONH bond

CH2CH2 [M + 1]⁻ = 1777 calcd. for C80H89Cl2F3N12O27•1.4HCl•11.9H2O C: 47.01%, H: 5.63%, N: 8.22%, Cl: 5.90%, F: 2.79% found: C: 47.17%, H: 5.59%, N: 7.64%, Cl: 5.93%, F: 2.66%

TABLE 61

bond CONH bond

CH2CH2 [M + 1]⁻ = 1747 calcd. for C82H92Cl2N12O27•1.9HCl•15.0H2O C: 47.17%, H: 5.98%, N: 8.05%, Cl: 6.62% found: C: 47.18%, H: 5.82%, N: 8.16%, Cl: 6.54%

bond CONH bond

CH2CH2 [M + 1]⁻ = 1776 calcd. for C80H84Cl2F4N12O26•1.3HCl•14.6H2O C: 46.04%, H: 5.53%, N: 8.05%, Cl: 5.61%, F: 3.64% found: C: 45.98%, H: 5.33%, N: 8.04%, Cl: 5.62%, F: 3.53%

bond CONH bond

CH2CH2 [M + 1]⁻ = 1742 calcd. for C79H84Cl3FN12O26•1.5HCl•13.9H2O C: 46.33%, H: 5.58%, N: 8.21%, Cl: 7.79%, F: 0.93% found: C: 46.32%, H: 5.54%, N: 8.27%, Cl: 7.75%, F: 0.95%

bond CONH bond

CH2CH2 [M + 1]⁻ = 1742 calcd. for C79H84Cl3FN12O26•1.2HCl•14.7H2O C: 46.25%, H: 5.63%, N: 8.19%, Cl: 7.26%, F: 0.93% found: C: 46.21%, H: 5.49%, N: 8.28%, Cl: 7.26%, F: 1.03%

TABLE 62

bond CONH bond

CH2CH2 [M + 1]⁻ = 1722 calcd. for C80H87Cl2FN12O26•1.9HCl•13.8H2O C: 47.09%, H: 5.75%, N: 8.24%, Cl: 6.78%, F: 0.93% found: C: 47.07%, H: 5.65%, N: 8.38%, Cl: 6.79%, F: 1.11%

bond CONH bond

CH2CH2 [M + 1]⁻ = 1757 calcd. for C79H84Cl4N12O26•1.8HCl•13.0H2O C: 46.08%, H: 5.47%, N: 8.16%, Cl: 9.99% found: C: 46.03%, H: 5.31%, N: 8.27%, Cl: 9.94%

bond CONH bond

CH2CH2 [M + 1]⁻ = 1787 calcd. for C81H87Cl2F3N12O27•1.7HCl•13.9H2O C: 46.31%, H: 5.59%, N: 8.00%, Cl: 6.24%, F: 2.71% found: C: 46.26%, H: 5.57%, N: 8.15%, Cl: 6.27%, F: 2.78%

bond CONH bond

CH2CH2 [M + 1]⁻ = 1775 calcd. for C80H84Cl2F4N12O26•1.9HCl•12.2H2O C: 46.52%, H: 5.38%, N: 8.14%, Cl: 6.69%, F: 3.68% found: C: 46.54%, H: 5.29%, N: 8.30%, Cl: 6.68%, F: 3.61%

TABLE 63

bond CONH bond

CH2CH2 [M + 1]⁻ = 1760 calcd. for C83H95Cl2N13O26•1.8HCl•12.2H2O C: 48.70%, H: 5.97%, N: 8.90%, Cl: 6.58% found: C: 48.68%, H: 5.89%, N: 9.05%, Cl: 6.49%

TABLE 64 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 3]⁺ =1718 calcd. for C83H92Cl2N10O26•1.0HCl•12.4H2O C: 50.25%, H: 5.96%, N: 7.06%, Cl: 6.08% found: C: 50.26%, H: 5.86%, N: 7.17%, Cl: 6.15%

bond CONH bond

CH2 [M + 1]⁻ =1756 calcd. for C85H96Cl2N12O25•2.4HCl•13.2H2O C: 49.04%, H: 6.04%, N: 8.07%, Cl: 7.49% found: C: 49.02%, H: 5.86%, N: 8.10%, Cl: 7.50%

bond CONH bond

CH2 [M + 1]⁻ =1867 calcd. for C88H100Cl2F3N13O25•3.1HCl•11.8H2O C: 48.19%, H: 5.82%, N: 8.30%, Cl: 8.24%, F: 2.60% found: C: 48.20%, H: 5.78%, N: 8.30%, Cl: 8.29%, F: 2.46%

TABLE 65

bond CONH bond

CH2 [M + 1]⁻ =1692 calcd. for C79H87Cl2N11O27•1.9HCl•11.2H2O C: 48.30%, H: 5.71%, N: 7.84%, Cl: 7.04% found: C: 48.29%, H: 5.58%, N: 7.81%, Cl: 6.96%

bond CONH bond

CH2 [M + 1]⁻ =1746 calcd. for C79H84Cl2F3N11O27•1.6HCl•9.9H2O C: 47.82%, H: 5.35%, N: 7.77%, Cl: 6.43%, F: 2.87% found: C: 47.79%, H: 5.18%, N: 7.79%, Cl: 6.51%, F: 2.76%

bond CONH bond

CH2 [M + 3]⁺ =1774 [M + 1]⁻ =1772 calcd. for C81H90Cl2F3N13O25•2.7HCl•10.7H2O C: 47.12%, H: 5.57%, N: 8.82%, Cl: 8.07%, F: 2.76% found: C: 47.13%, H: 5.40%, N: 8.83%, Cl: 8.02%, F: 2.65%

bond CONH bond

CH2 [M + 1]⁻ =1808 calcd. for C89H96Cl2N10O27•1.5HCl•11H2O C: 51.85%, H: 5.84%, N: 6.79%, Cl: 6.02% found: C: 51.89%, H: 5.59%, N: 6.77%, Cl: 5.99%

bond CONH bond

CH2 [M + 1]⁻ =1797 calcd. for C87H95Cl2N11O27•1.7HCl•11.2H2O C: 50.69%, H: 5.82%, N: 7.47%, Cl: 6.36% found: C: 50.72%, H: 5.78%, N: 7.46%, Cl: 6.33%

TABLE 66

bond CONH bond

CH2 [M + 1]⁻ =1759 calcd. for C82H87Cl2F3N10O26•1.9HCl•11.1H2O C: 51.07%, H: 5.94%, N: 7.01%, Cl: 6.21% found: C: 51.07%, H: 5.75%, N: 7.12%, Cl: 6.17%

bond CONH bond

CH2 [M + 1]⁻ =1787 calcd. for C87H100Cl2N10O27•2HCl•10.2H2O C: 51.09%, H: 6.03%, N: 6.85%, Cl: 6.93% found: C: 51.06%, H: 5.98%, N: 6.95%, Cl: 6.87%

bond CONH bond

CH2 [M + 1]⁻ =1771 calcd. for C87H100Cl2N10O26•1.6HCl•9.7H2O C: 52.10%, H: 6.08%, N: 6.98%, Cl: 6.36% found: C: 52.09%, H: 6.07%, N: 7.11%, Cl: 6.33%

bond CONH bond

CH2 [M + 1]⁻ =1835 calcd. for C91H101Cl2N11O26•2.8HCl•10.6H2O C: 51.34%, H: 5.92%, N: 7.24%, Cl: 7.99% found: C: 51.28%, H: 5.84%, N: 7.47%, Cl: 7.91%

bond CONH bond

CH2 [M + 3]⁺ =1658 [M + 1]⁻ =1660 calcd for C82H87Cl2F3N10O26•1.9HCl•11.1H2O C: 48.83%, H: 5.73%, N: 7.93%, Cl: 7.30% found: C: 48.85%, H: 5.66%, N: 7.85%, Cl: 7.31%

TABLE 67

bond CONH bond

CH2 [M + 1]⁻ = 1762 calcd. for C79H84Cl2F3N11O26S•1.4HCl•11.1H2O C: 47.10%, H: 5.38%, N: 7.65%, Cl: 5.98%, F: 2.83%, S: 1.59% found: C: 47.09%, H: 5.37%, N: 7.60%, Cl: 5.92%, F: 2.74%, S: 1.50%

bond CONH bond

CH2 [M + 1]⁻ = 1755 calcd. for C82H87Cl2F3N10O26•1.9HCl•11.1H2O C: 48.36%, H: 5.62%, N: 6.88%, Cl: 6.09%, F: 2.80% found: C: 48.32%, H: 5.53%, N: 6.96%, Cl: 6.06%, F: 2.78%

bond CONH bond

CH2 [M + 1]⁻ = 1743 calcd. for C82H87Cl2F3N10O26•1.9HCl•11.1H2O C: 48.22%, H: 5.46%, N: 7.73%, Cl: 5.69%, F: 2.86% found: C: 48.19%, H: 5.36%, N: 7.78%, Cl: 5.76%, F: 2.74%

bond NHCO bond

CH2 [M + 1]⁻ = 1748 calcd. for C82H87Cl2F3N10O26•1.9HCl•11.1H2O C: 46.08%, H: 5.45%, N: 6.80%, Cl: 6.89%, F: 2.77%, S: 1.56 found: C: 46.04%, H: 5.35%, N: 6.96%, Cl: 6.94%, F: 2.65%, S: 1.30

bond NHCO bond

CH2 [M + 1]⁻ = 1732 calcd. for C79H83Cl2F3N10O27•1.9HCl•12.5H2O C: 46.81%, H: 5.47%, N: 6.91%, Cl: 6.82%, F: 2.81% found: C: 46.77%, H: 5.39%, N: 7.01%, Cl: 6.75%, F: 2.67%

TABLE 68

bond CONH bond

CH2 [M + 1]⁻ = 1742 calcd. for C80H84Cl2F3N11O26•1.9HCl•12.5H2O C: 47.15%, H: 5.48%, N: 7.56%, Cl: 6.78%, F: 2.80% found: C: 47.14%, H: 5.43%, N: 7.67%, Cl: 6.78%, F: 2.70%

bond CONH bond

CH2 [M + 1]⁻ = 1820 calcd. for C81H84Cl2F3BrN10O26•2HCl•14.3H2O C: 45.21%, H: 5.37%, N: 6.51%, Cl: 6.59%, F: 2.65%, Br: 3.71% found C: 45.18%, H: 5.14%, H: 6.71%, Cl: 6.64%, F: 2.57%, Br: 3.49%

bond CONH bond

CH2 [M + 1]⁻ = 1819 calcd. for C86H88Cl2F3N11O26•1.5HCl•15.4H2O C: 48.00%, H: 5.64%, N: 7.16%, Cl: 5.77%, F: 2.65% found: C: 47.96%, H: 5.64%, N: 7.24%, Cl: 5.78%, F: 2.60%

bond CONH bond

CH2 [M + 1]⁻ = 1772 calcd. for C82H87Cl2F3N10O27•1.3HCl•13.5H2O C: 47.65%, H: 5.61%, N: 6.78%, Cl: 6.00%, F: 2.76% found C: 47.65%, H: 5.59%, N: 6.91%, Cl: 5.99%, F: 2.73%

bond CONH bond

CH2 [M + 1]⁻ = 1758 calcd. for C81H85Cl2F3H10O27•1.7HCl•13.2H2O C: 47.27%, H: 5.54%, N: 6.81%, Cl: 6.37%, F: 2.77% found: C: 47.25%, H: 5.35%, N: 6.95%, Cl: 6.30%, F: 2.72%

TABLE 69

bond CONH bond

CH2 [M + 1]⁻ =1878 calcd. for C89H93Cl2F3N10O28•1.8HCl•13.5H2O C: 48.87%, H: 5.61%, N: 6.40%, Cl: 6.16%, F: 2.6% found: C: 48.85%, H: 5.42%, N: 647.%, Cl: 6.07%, F: 2.58%

bond CONH bond

CH2 [M + 1]⁻ =1771 calcd. for C87H96Cl2F3N11O28•2.5HCl•14.6H2O C: 46.95%, H: 5.78%, N: 6.92%, Cl: 7.17%, F: 2.56% found: C: 46.92%, H: 5.70%, N: 6.99%, Cl: 7.17%, F: 2.51%

bond CONH bond

CH2 [M + 1]⁻ =1799 calcd. for C84H92Cl2F3N11O26•2.2HCl•16.4H2O C: 46.61%, H: 5.76%, N: 7.12%, Cl: 8.02%, F: 2.63% found: C: 46.60%, H: 5.67%, N: 7.28%, Cl: 7.97%, F: 2.53%

bond CONH bond

CH2 [M + 1]⁻ =1758 calcd. for C81H85Cl2F3N10O27•2.0HCl•12.0H2O C: 46.87%, H: 5.79%, N: 6.91%, Cl: 7.16%, F: 2.56% found: C: 46.85%, H: 5.65%, N: 6.96%, Cl: 7.21%, F: 2.53%

bond CONH bond

CH2 [M + 1]⁻ =1841 calcd. for C86H94Cl2F3N11O27•2.4HCl•15.5H2O C: 46.77%, H: 5.81%, N: 6.98%, Cl: 7.06%, F: 2.58% found: C: 46.76%, H: 5.63%, N: 7.10%, Cl: 7.06%, F: 2.68%

TABLE 70

bond CONH bond

CH2 [M + 3]⁺ =1872 calcd. for C87H96Cl2F3N11O28•2.5HCl•14.8H2O C: 48.62%, H: 5.53%, N: 6.91%, Cl: 6.83%, F: 2.81% found: C: 48.63%, H: 5.40%, N: 6.96%, Cl: 6.88%, F: 2.67%

bond CONH bond

CH2 [M + 1]⁻ =1786 calcd. for C82H85Cl2F3N10O28•2.1HCl•14.4H2O C: 46.40%, H: 5.50%, N: 6.60%, Cl: 6.85%, F: 2.69% found: C: 46.39%, H: 5.43%, N: 6.78%, Cl: 6.64%, F: 2.62%

bond CONH bond

CH2 [M + 1]⁻ =1812 calcd. for C84H87Cl2F3N10O28•2.0HCl•13.3H2O C: 47.48%, H: 5.48%, N: 6.59%, Cl: 6.67%, F: 2.68% found: C: 47.45%, H: 5.37%, N: 6.71%, Cl: 6.73%, F: 2.79%

bond CONH bond

CH2 [M + 1]⁻ =1881 calcd. for C88H94Cl2F3N11O28•2.0HCl•13.0H2O C: 48.29%, H: 5.62%, N: 7.04%, Cl: 6.48%, F: 2.60% found: C: 48.46%, H: 5.55%, N: 7.12%, Cl: 6.55%, F: 2.73%

bond NHCO bond

CH2 [M + 1]⁻ =1748 calcd. for C78H82Cl2F3N11O26S1•2.0HCl•13.0H2O C: 45.55%, H: 5.39%, N: 7.49%, Cl: 6.90%, F: 2.77%, S: 1.56% found: C: 45.55%, H: 5.40%, N: 7.49%, Cl: 6.82%, F: 2.93%, S: 1.75%

TABLE 71

bond CONH bond

CH2 [M + 1]⁻ = 1807 calcd. for C85H87Cl2F3N10O27•2.0HCl•12.8H2O C: 48.34%, H: 5.47%, N: 6.63%, Cl: 6.71%, F: 2.70% found C: 48.32%, H: 5.50%, N: 6.68%, Cl: 6.72%, F: 2.85%

bond CONH bond

CH2 [M + 1]⁻ = 1743 calcd. for C80H84Cl2F3N11O26•1.3HCl•14.5H2O C: 46.82%, H: 5.61%, N: 7.51%, Cl: 5.70%, F: 2.78% found: C: 46.77%, H: 5.38%, N: 7.57%, Cl: 5.76%, F: 2.75%

bond CONH bond

CH2 [M + 1]⁻ = 1799 calcd. for C83H88Cl2F3N11O27•1.9HCl•15.9H2O C: 46.25%, H: 5.69%, N: 7.15%, Cl: 6.42%, F: 2.64% found: C: 46.26%, H: 5.67%, N: 7.24%, Cl: 6.48%, F: 2.59%

bond CONH bond

CH2 [M + 1]⁻ = 1835 calcd. for C82H88Cl2F3N11O28S1•1.9HCl•13.9H2O C: 45.70%, H: 5.50%, N: 7.15%, Cl: 6.42%, F: 2.64%, S: 1.49% found: C: 45.69%, H: 5.43%, N: 7.18%, Cl: 6.45%, F: 2.56%, S: 1.37%

bond CONH bond

CH2 [M + 1]⁻ = 1787 calcd. for C81H84Cl2F3N11O28•1.9HCl•14.0H2O C: 46.13%, H: 5.44%, N: 7.31%, Cl: 6.56%, F: 2.70% found: C: 46.11%, H: 5.37%, N: 7.31%, Cl: 6.53%, F: 2.63%

TABLE 72

bond CONH bond

CH2 [M + 1]⁻ = 1767 calcd. for C82H84Cl2F3N11O26•2.0HCl•13.8H2O C: 47.15%, H: 5.48%, N: 7.38%, Cl: 6.79%, F: 2.73% found: C: 47.12%, H: 5.43%, N: 7.47%, Cl: 6.80%, F: 2.72%

bond CONH bond

CH2 [M + 1]⁻ = 1799 calcd. for C83H87Cl2F3N10O28•1.7HCl•13.6H2O C: 47.30%, H: 5.54%, N: 6.65%, Cl: 6.22%, F: 2.70% found: C: 47.28%, H: 5.48%, N: 6.71%, Cl: 6.18%, F: 2.69%

bond CONH bond

CH2 [M + 1]⁻ = 1799 calcd. for C84H92Cl2F3N11O26•2.9HCl•14.9H2O C: 46.41%, H: 5.78%, N: 7.09%, Cl: 7.99%, F: 2.62 found: C: 46.36%, H: 5.71%, N: 7.28%, Cl: 8.02%, F: 2.49%

bond CONH bond

CH2 [M + 1]⁻ = 1825 calcd. for C86H94Cl2F3N11O26•2.8HCl•13.5H2O C: 47.58%, H: 5.75%, N: 7.10%, Cl: 7.84%, F: 2.63% found: C: 47.53%, H: 5.65%, N: 7.29%, Cl: 7.88%, F: 2.63%

bond CONH bond

CH2 [M + 1]⁻ = 1813 calcd. for C85H94Cl2F3N11O26•2.8HCl•13.1H2O C: 47.45%, H: 5.76%, N: 7.16%, Cl: 7.91%, F: 2.65% found: C: 47.40%, H: 5.68%, N: 7.35%, Cl: 7.98%, F: 2.66%

TABLE 73

bond CONH bond

CH2 [M + 1]⁻ =1822 calcd. for C85H89Cl2F3N12O26•2.8HCl•13.7H2O C: 47.01%, H: 5.53%, N: 7.74%, Cl: 7.84%, F: 2.62% found: C: 46.98%, H: 5.50%, N: 7.90%, Cl: 7.90%, F: 2.58%

bond CONH bond

CH2 [M + 1]⁻ =1840 calcd. for C86H95Cl2F3N12O26•2.5HCl•15.3H2O C: 46.79%, H: 5.85%, N: 7.61%, Cl: 7.23%, F: 2.58% found: C: 46.78%, H: 5.90%, N: 7.74%, Cl: 7.21%, F: 2.49%

bond CONH bond

CH2 [M + 1]⁻ =1743 calcd. for C80H84Cl2F3N11O26•1.6HCl•13.4H2O C: 47.03%, H: 5.54%, N: 7.54%, Cl: 6.25%, F: 2.79% found: C: 46.99%, H: 5.36%, N: 7.65%, Cl: 6.22%, F: 2.85%

bond CONH bond

CH2 [M + 1]⁻ =1733 calcd. for C78H82Cl2F3N11O25S1•1.5HCl•12.3H2O C: 46.61%, H: 5.42%, N: 7.67%, Cl: 6.17%, F: 2.84%, S: 1.60% found: C: 46.58%, H: 5.35%, N: 7.88%, Cl: 6.22%, F: 2.92%, S: 1.72%

bond CONH bond

CH2 [M + 1]⁻ =1721 calcd. for C81H91Cl2N10O25S1•1.7HCl•12.0H2O C: 48.65%, H: 5.88%, N: 7.70%, Cl: 6.56%, S: 1.60% found: C: 48.63%, H: 5.86%, N: 7.75%, Cl: 6.63%, S: 1.65%

TABLE 74

bond CONH bond

CH2 [M + 1]⁻ =1692 calcd. for C79H87Cl2N11O25S1•1.9HCl•11.1H2O C: 47.26%, H: 5.83%, N: 7.67%, Cl: 6.89%, S: 1.60% found: C: 47.26%, H: 5.83%, N: 7.67%, Cl: 6.84%, S: 1.54%

bond CONH bond

CH2 [M + 1]⁻ =1693 calcd. for C79H87Cl2N11O25S1•1.7HCl•13.2H2O C: 47.60%, H: 5.82%, N: 7.73%, Cl: 6.58%, S: 1.61% found: C: 47.54%, H: 5.62%, N: 7.86%, Cl: 6.64%, S: 1.53%

bond CONH bond

CH2 [M + 1]⁻ =1727 calcd. for C79H83Cl4N11O25•1.3HCl•13.4H2O C: 47.04%, H: 5.55%, N: 7.64%, Cl: 9.32% found: C: 47.02%, H: 5.53%, N: 7.72%, Cl: 9.27%

bond CONH bond

CH2 [M + 1]⁻ =1770 calcd. for C82H89Cl2F3N12O25•3.5HCl•14.1H2O C: 45.76%, H: 5.65%, N: 7.81%, Cl: 9.06%, F: 2.65% found: C: 45.71%, H: 5.30%, N: 7.89%, Cl: 9.00%, F: 2.71%

bond NHCO NH

CH2 [M + 1]⁻ =1758 calcd. for C80H85Cl2F3N12O26•1.5HCl•13.3H2O C: 46.81%, H: 5.55%, N: 8.19%, Cl: 6.04%, F: 2.78% found: C: 46.72%, H: 5.40%, N: 8.35%, Cl: 6.02%, F: 2.86%

TABLE 75

bond CONH bond

CH2 [M + 1]⁻ =1824 calcd. for C85H94Cl4N12O25•2.4HCl•14.5H2O C: 46.95%, H: 5.81%, N: 7.73%, Cl: 10.44% found: C: 46.92%, H: 5.69%, N: 7.80%, Cl: 10.46%

bond CONH bond

CH2 [M + 1]⁻ =1786 calcd. for C82H89Cl2F3N12O26•2.2HCl•14.1H2O C: 46.44%, H: 5.67%, N: 7.93%, Cl: 7.02%, F: 2.69% found: C: 46.37%, H: 5.49%, N: 8.01%, Cl: 7.05%, F: 2.67%

bond CONH bond

CH2 [M + 1]⁻ =1810 calcd. for C83H85Cl2F3N12O27•2.3HCl•11.0H2O C: 47.64%, H: 5.26%, N: 8.03%, Cl: 7.29%, F: 2.72% found: C: 47.75%, H: 5.36%, N: 8.05%, Cl: 7.33%, F: 1.02%

bond CONH bond

CH2 [M + 1]⁻ =1801 calcd. for C82H86Cl2F3N11O28•1.6HCl•13.8H2O C: 46.71%, H: 5.51%, N: 7.31%, Cl: 6.05%, F: 2.70% found: C: 46.65%, H: 5.49%, N: 7.47%, Cl: 6.08%, F: 2.61%

bond

CH2 [M + 1]⁻ =1810 calcd. for C85H92Cl2F3N11O26•2.2HCl•20.6H2O C: 45.11%, H: 6.03%, N: 6.81%, Cl: 6.58%, F: 2.52% found: C: 45.10%, H: 5.98%, N: 6.87%, Cl: 6.58%, F: 2.46%

TABLE 76

bond

CH2 [M + 1]⁻ =1810 calcd. for C85H92Cl2F3N11O26•2.0HCl•13.1H2O C: 48.14%, H: 5.71%, N: 7.27%, C: 6.69%, F: 2.69% found: C: 48.15%, H: 5.62%, N: 7.34%, Cl: 6.64%, F: 2.88%

TABLE 77 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 1]⁻ =1783 calcd. for C87H100Cl2N12O25•3HCl•13H2O C: 58.55%, H: 5.65%, N: 9.42%, Cl: 3.97% found: C: 49.28%, H: 6.01%, N: 8.06%, Cl: 7.96%

bond CONH bond

CH2 [M + 3]⁺ =1799 [M + 1]⁻ =1797 calcd. for C87H98Cl2N12O26•2HCl•11.5H2O C: 58.09%, H: 5.49%, N: 9.34%, Cl: 3.94% found: C: 50.06%, H: 5.92%, N: 8.13%, Cl: 7.12%

TABLE 78

bond CONH bond

CH2 [M + 3]⁺ =1867 [M + 1]⁻ =1865 calcd. for C88H97Cl2F3N12O26•3HCl•14H2O C: 56.62%, H: 5.24%, N: 9.00%, Cl: 3.8%, F: 3.05% found: C: 47.63%, H: 5.62%, N: 7.63%, Cl: 7.63%, F: 2.43%

bond CONH bond

CH2 [M + 1]⁻ =1809 calcd. for C82H84Cl2F6N10O26•2HCl•10H2O C: 54.4%, H: 4.68%, N: 7.44%, Cl: 3.92%, F: 6.3% found: C: 47.89%, H: 5.07%, N: 7.02%, Cl: 6.68%, F: 5.40%

bond CONH bond

CH2 [M + 1]⁻ =1880 calcd. for C88H98Cl2F3N13O26•3HCl•17H2O C: 56.17%, H: 5.25%, N: 9.68%, Cl: 3.77%, F: 3.03% found: C: 46.04%, H: 5.69%, N: 7.99%, Cl: 7.98%, F: 2.38%

bond CONH bond

CH2 [M + 1]⁻ =1839 calcd. for C86H95Cl2F3N12O26•3HCl•13H2O C: 56.12%, H: 5.2%, N: 9.13%, Cl: 3.85%, F: 3.10% found: C: 47.39%, H: 5.43%, N: 7.75%, Cl: 7.91%, F: 2.56%

TABLE 79

bond CONH bond

CH2 [M + 1]⁻ =1825 calcd. for C85H93Cl2F3N12O26•2.5HCl•13.5H2O C: 55.89%, H: 5.13%, N: 9.20%, Cl: 3.88%, F: 3.12% found: C: 47.03%, H: 5.52%, N: 7.74%, Cl: 7.67%, F: 2.55%

bond CONH bond

CH2 [M + 3]⁺ =1842 [M + 1]⁻ =1840 calcd. for C86H94Cl2F3N11O27•2.5HCl•14.5H2O C: 56.09%, H: 5.14%, N: 8.37%, Cl: 3.85%, F: 3.09% found: C: 46.96%, H: 5.673%, N: 7.15%, Cl: 7.65%, F: 2.60%

bond CONH bond

CH2 [M + 3]⁺ =1801 [M + 1]⁻ =1799 calcd. for C83H87Cl2F3N10O28•2HCl•11H2O C: 55.37%, H: 4.87%, N: 7.78%, Cl: 3.94%, F: 3.17% found: C: 48.01%, H: 5.42%, N: 6.82%, Cl: 6.77%, F: 2.75%

bond CONH bond

CH2 [M + 3]⁺ =1869 [M + 1]⁻ =1867 calcd. for C87H95Cl2F3N12O27•2.5HCl•15.5H2O C: 55.92%, H: 5.12%, N: 8.99%, Cl: 3.79%, F: 3.05% found: C: 46.48%, H: 5.95%, N: 7.53%, Cl: 7.33%, F: 2.50%

TABLE 80

bond CONH bond

CH2 [M + 1]⁻ = 1854 calcd. for C86H92Cl2F3N11O28•2.5HCl•13.5H2O C: 55.66%, H: 5.00%, N: 8.30%, Cl: 3.82%, F: 3.07% found: C: 47.73%, H: 5.78%, N: 6.82%, Cl: 6.21%, F: 2.65%

bond CONH bond

CH2 [M + 1]⁻ = 1784 calcd. for C82H86Cl2F3N11O27•2HCl•14H2O C: 55.16%, H: 4.85%, N: 8.63%, Cl: 3.97%, F: 3.19% found: C: 46.7%, H: 5.53%, N: 7.45%, Cl: 6.64%, F: 2.67%

bond CONH bond

CH2 [M + 3]⁺ = 1855 calcd. for C87H97Cl2F3N12O26•2.5HCl•5H2O C: 56.34%, H: 5.27%, N: 9.06%, Cl: 3.82%, F: 3.07% found: C: 47.13%, H: 5.72%, N: 7.65%, Cl: 7.33%, F: 2.55%

bond CONH bond

CH2 [M + 1]⁻ = 1785 calcd. for C86H98Cl2N12O26•2HCl•14H2O C: 57.81%, H: 5.53%, N: 9.41%, Cl: 3.97% found: C: 48.77. H: 5.98%, N: 7.97%, Cl: 6.86%

TABLE 81

bond CONH bond

CH2 [M + 1]⁻ = 1743 calcd. for C84H96Cl2N12O25•2.5HCl•15H2O C: 57.83%, H: 5.55%, N: 9.63%, Cl: 4.06% found: C: 47.92, H: 6.13%, N: 7.95%, Cl: 7.59%

bond NHCO bond

CH2 [M + 1]⁻ = 1810 calcd. for C85H92Cl2F3N11O26•2HCl•13H2O C: 56.35%, H: 5.12%, N: 8.50%, Cl: 3.91%, F: 3.15 found: C: 48.20, H: 5.63%, N: 7.19%, Cl: 6.76%, F: 2.73

bond NHCO bond

CH2 [M + 1]⁻ = 1768 calcd. for C83H90Cl2F3N11O25•2HCl•16H2O C: 56.35%, H: 5.12%, N: 8.50%, Cl: 3.91%, F: 3.22% found: C: 48.20, H: 5.63%, N: 7.19%, Cl: 6.76%, F: 2.83%

bond NHCO bond

CH2 [M + 1]⁻ = 1823 calcd. for C86H95Cl2F3N12O25•3HCl•15H2O C: 56.61%, H: 5.25%, N: 9.21%, Cl: 3.89%, F: 3.12% found: C: 46.94. H: 5.80%, N: 7.86%, Cl: 7.79%, F: 2.66%

TABLE 82

bond CONH bond

CH2 [M + 1]⁻ = 1810 calcd. for C84H91Cl4N11O26•2HCl•11H2O C: 55.66%, H: 5.06%, N: 8.50%, Cl: 7.82% found: C: 48.25%, H: 5.64%, N: 7.45%, Cl: 10.13%

bond CONH bond

CH2 [M + 1]⁻ = 1768 calcd. for C82H89Cl4N11O25•1.5HCl•13H2O C: 55.63%, H: 5.07%, N: 8.7%, Cl: 8.01% found: C: 47.73%, H: 5.48%, N: 7.67%, Cl: 9.7%

bond CONH bond

CH2 [M + 1]⁻ = 1825 calcd. for C84H92Cl4N12O26•1.5HCl•13.5H2O C: 55.21%, H: 5.07%, N: 9.20%, Cl: 7.76% found: C: 47.75%, H: 5.58%, N: 8.10%, Cl: 8.87%

TABLE 83 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 1]⁻ =1742 calcd. for C85H94Cl2N10O26•2.0HCl•15.8H2O C: 48.61%, H: 6.12%, N: 6.67%, Cl: 6.75% found: C: 48.55%, H: 6.05%, N: 6.76%, Cl: 6.80%

bond CONH bond

CH2 [M + 1]⁻ =1732 calcd. for C83H92Cl2N10O27•1.5HCl•12.4H2O C: 49.58%, H: 5.93%, N: 6.97%, Cl: 6.17% found: C: 49.56%, H: 5.86%, N: 6.96%, Cl: 6.18%

bond CONH bond

CH2 [M + 1]⁻ =1755 calcd. for C85H93Cl2N11O26•1.5HCl•11.3H2O C: 50.69%, H: 5.86%, N: 7.65%, Cl: 6.16% found: C: 50.67%, H: 5.79%, N: 7.72%, Cl: 6.24%

bond CONH bond

CH2 [M + 1]⁻ =1748 calcd. for C78H82Cl2F3N11O26S•1.8HCl•11.8H2O C: 46.20%, H: 5.34%, N: 7.60%, Cl: 6.64%, F: 2.81%, S: 1.58% found: C: 46.19%, H: 5.37%, N: 7.71%, Cl: 6.59%, F: 2.86%, S: 1.69%

TABLE 84

bond CONH bond

CH2 [M + 3]⁺ =1844 [M + 1]⁻ =1842 calcd. for C85H93Cl2F3N12O27•1.7HCl•15.2H2O C: 46.86%, H: 5.79%, N: 7.72%, Cl: 6.02% found: C: 46.86%, H: 5.75%, N: 7.77%, Cl: 5.98%

bond CONH bond

CH2 [M + 1]⁻ =1873 calcd. for C87H98Cl2F3N11O28•2.2HCl•13.4H2O C: 47.60%, H: 5.83%, N: 7.02%, Cl: 6.78%, F: 2.60% found: C: 47.36%, H: 5.89%, N: 7.00%, Cl: 6.71%, F: 2.90%

bond CONH bond

CH2 [M + 1]⁻ =1904 calcd. for C89H95Cl2F3N14O26•2.5HCl•17.0H2O C: 46.43%, H: 5.76%, N: 8.52%, Cl: 6.93%, F: 2.48% found: C: 46.38%, H: 5.67%, N: 8.64%, Cl: 6.92%, F: 2.72%

bond CONH bond

CH2 [M + 1]⁻ =1854 calcd. for C87H97Cl2F3N12O26•2.7HCl•14.4H2O C: 47.23%, H: 5.85%, N: 7.60%, Cl: 7.53%, F: 2.58% found: C: 47.25%, H: 5.79%, N: 7.69%, Cl: 7.53%, F: 2.57%

bond CONH bond

CH2 [M + 1]⁻ =1894 calcd. for C90H101Cl2F3N12O26•2.6HCl•15.1H2O C: 47.80%, H: 5.96%, N: 7.43%, Cl: 7.21%, F: 2.52% found: C: 47.80%, H: 5.89%, N: 7.44%, Cl: 7.24%, F: 2.62%

bond CONH bond

CH2 [M + 3]⁺ =1857 [M + 1]⁻ =1855 calcd. for C86H96Cl2F3N13O26•3.0HCl•13.6H2O C: 46.74%, H: 5.76%, N: 8.24%, Cl: 8.02%, F: 2.58% found: C: 46.76%, H: 5.76%, N: 8.28%, Cl: 7.96%, F: 2.60%

TABLE 85

bond CONH bond

CH2 [M + 1]⁻ =1827 calcd. for C85H92Cl2F3N11O27•1.7HCl•13.5H2O C: 47.87%, H: 5.70%, N: 7.22%, Cl: 6.15%, F: 2.67% found: C: 47.85%, H: 5.68%, N: 7.28%, Cl: 6.17%, F: 2.82%

bond CONH bond

CH2 [M + 1]⁻ =1827 calcd. for C85H92Cl2F3N11O27•1.9HCl•11.1H2O C: 48.69%, H: 5.58%, N: 7.35%, Cl: 6.59%, F: 2.72% found: C: 48.68%, H: 5.54%, N: 7.43%, Cl: 6.67%, F: 2.66%

bond CONH bond

CH2 [M + 1]⁻ =1845 calcd. for C85H94Cl2F3N11O28•2.2HCl•11.5H2O C: 47.86%, H: 5.63%, N: 7.22%, Cl: 6.98%, F: 2.67% found: C: 47.84%, H: 5.68%, N: 7.29%, Cl: 7.06%, F: 2.56%

bond CONH bond

CH2 [M + 1]⁻ =1854 calcd. for C86H96Cl4N12O26•3.2HCl•11.7H2O C: 47.32%, H: 5.66%, N: 7.70%, Cl: 11.69% found: C: 47.31%, H: 5.74%, N: 7.78%, Cl: 11.65%

bond CONH bond

CH2 [M + 1]⁻ =1882 calcd. for C88H100Cl4N12O26•2.8HCl•12.1H2O C: 47.96%, H: 5.81%, N: 7.63%, Cl: 10.94% found: C: 47.94%, H: 5.77%, N: 7.83%, Cl: 11.00%

bond CONH bond

CH2 [M + 1]⁻ =1838 calcd. for C86H96Cl4N12O25•3.0HCl•13.8H2O C: 47.00%, H: 5.81%, N: 7.65%, Cl: 11.29% found: C: 46.99%, H: 5.64%, N: 7.79%, Cl: 11.21%

TABLE 86

bond NHCO NH

CH2 [M + 3]⁺ =1859 [M +1]⁻ =1857 calcd. for C85H94Cl2F3N13O27•2.4HCl•12.7H2O C: 46.96%, H: 5.65%, N: 8.38%, Cl: 7.18%, F: 2.62% found: C: 46.89%, H: 5.57%, N: 8.55%, Cl: 7.21%, F: 2.59%

bond CONH bond

CH2 [M + 1]⁻ =1842 calcd. for C85H93Cl2F3N12O27•1.5HCl•13.9H2O C: 47.53%, H: 5.74%, N: 7.83%, Cl: 5.78%, F: 2.65% found: C: 47.50%, H: 5.54%, N: 7.84%, Cl: 5.80%, F: 2.64%

bond NHCO NH

CH2 [M + 1]⁻ =1857 calcd. for C85H94Cl2F3N13O27•1.8HCl•11.6H2O C: 47.88%, H: 5.63%, N: 8.54%, Cl: 6.32%, F: 2.67% found: C: 47.88%, H: 5.56%, N: 8.51%, Cl: 6.36%, F: 2.61%

bond CONH bond

CH2 [M + 1]⁻ =1842 calcd. for C85H93Cl3F3N12O27•1.3HCl•13.8H2O C: 47.74%, H: 5.75%, N: 7.86%, Cl: 5.47%, F: 2.67% found: C: 47.72%, H: 5.67%, N: 7.94%, Cl: 5.42%, F: 2.64%

bond CONH bond

CH2 [M + 3]⁺ =1802 [M +1]⁻ =1800 calcd. for C83H91Cl2F3N12O26•1.6HCl•13.7H2O C: 47.34%, H: 5.74%, N: 7.98%, Cl: 6.06%, F: 2.71% found: C: 47.29%, H: 5.73%, N: 8.10%, Cl: 6.12%, F: 2.84%

bond CONH bond

CH2 [M + 3]⁺ =1832 [M +1]⁻ =1830 calcd. for C88H102Cl2N12O27•1.6HCl•11.4H2O C: 50.46%, H: 6.08%, N: 8.03%, Cl: 6.09% found: C: 50.46%, H: 5.95%, N: 8.11%, Cl: 6.06%

TABLE 87

bond CONH bond

CH2 [M + 3]⁺ =1844 [M + 1]⁻ =1842 calcd. for C85H93Cl2F3N12O27•1.9HCl•11.6H2O C: 48.14%, H: 5.61%, N: 7.93%, Cl: 6.52%, F: 2.69% found: C: 48.11%, H: 5.60%, N: 8.03%, Cl: 6.44%, F: 2.84%

bond CONH bond

CH2 [M + 3]⁺ =1842 [M + 1]⁻ =1840 calcd. for C85H94Cl2F2N12O26S•2.0HCl•9.8H2O C: 48.84%, H: 5.57%, N: 8.04%, Cl: 6.78%, F: 1.82%, S: 1.53% found: C: 48.83%, H: 5.47%, N: 8.10%, Cl: 6.79%, F: 1.96%, S: 1.53%

bond NHCO NH

CH2 [M + 3]⁺ =1816 [M + 1]⁻ =1814 calcd. for C83H92Cl2F3N13O26•1.9HCl•10.8H2O C: 47.94%, H: 5.60%, N: 8.76%, Cl: 6.65%, F: 2.74% found: C: 47.93%, H: 5.61%, N: 8.80%, Cl: 6.72%, F: 2.53%

TABLE 88 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 1]⁻ =1739 calcd. for C81H86Cl2F2N10O25S•1.3HCl•8.3H2O C: 50.21%, H: 5.41%, N: 7.23%, Cl: 6.04%, F: 1.96%, S: 1.65% found: C: 50.35%, H: 5.50%, N: 6.75%, Cl: 6.05%, F: 1.72%, S: 1.39%

bond CONH bond

CH2 [M + 3]⁺ =1841 [M + 1]⁻ =1839 calcd. for C86H95Cl2F3N12O26•2.4HCl•10.3H2O C: 48.87%, H: 5.63%, N: 7.95%, Cl: 7.38%, F: 2.70% found: C: 48.99%, H: 5.67%, N: 7.45%, Cl: 7.43%, F: 2.18%

bond CONH bond

CH2 [M + 3]⁺ =1828 [M + 1]⁻ =1826 calcd. for C85H92Cl2F3N11O27•1.9HCl•11.8H2O C: 48.40%, H: 5.61%, N: 7.30%, Cl: 6.55%, F: 2.70% found: C: 48.38%, H: 5.54%, N: 7.41%, Cl: 6.56%, F: 2.55%

bond CONH bond

CH2 [M + 1]⁻ =1841 calcd. for C86H97Cl2F3N12O26•0.8HCl•16.2H2O C: 47.74%, H: 6.07%, N: 7.77%, Cl: 4.59%, F: 2.63% found: C: 47.78%, H: 5.78%, N: 7.98%, Cl: 4.76%, F: 1.73%

TABLE 89

bond CONH bond

CH2 [M + 3]⁺ =1855 [M + 1]⁻ =1853 calcd. for C87H97Cl2F3N12O26•2.7HCl•12.7H2O C: 47.89%, H: 5.78%, N: 7.70%, Cl: 7.64%, F: 2.61% found C: 48.82%, H: 5.81%, N: 6.72%, Cl: 7.78%, F: 2.07%

bond CONH bond

CH2 [M + 1]⁻ =1857 calcd. for C87H100Cl3F3N12O26•1.1HCl•10.6H2O C: 49.19%, H: 5.80%, N: 7.91%, Cl: 6.84%, F: 2.68% found: C: 49.39%, H: 5.84%, N: 7.37%, Cl: 6.82%, F: 2.45%

bond CONH bond

CH2 [M + 1]⁻ =1938 calcd. for C91H104Cl2F3N13O27•3.7HCl•14.8H2O C: 46.68%, H: 5.91%, N: 7.78%, Cl: 8.63%, F: 2.43% found: C: 46.75%, H: 5.91%, N: 7.64%, Cl: 8.59%, F: 2.19%

TABLE 90 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 1]⁻ =1745 calcd. for C79H85Cl2F3N12O26•1.9HCl•12.5H2O C: 46.49%, H: 5.53%, Cl: 6.77, F: 2.79, N: 8.24% found: C: 46.46%, H: 5.47%, Cl: 6.75, F: 2.69, N: 8.33%

bond CONH bond

CH2 [M + 1]⁻ =1773 calcd. for C81H89Cl2F3N12O26•2.0HCl•14.9H2O C: 45.98%, H: 5.75%, Cl: 6.70, F: 2.69, N: 7.94% found: C: 45.95%, H: 5.73%, Cl: 6.90, F: 2.66, N: 7.97%

bond CONH bond

CH2 [M + 1]⁻ =1802 calcd. for C82H92Cl2F3N13O26•2.8HCl•16.0H2O C: 44.89%, H: 5.83%, Cl: 7.76, F: 2.60, N: 8.30% found: C: 44.93%, H: 5.81%, Cl: 7.76, F: 2.67, N: 8.26%

TABLE 91

bond CONH bond

CH2 [M + 1]⁺ = 1789 calcd. for C81H89Cl2F3N12O27•1.8HCl•14.5H2O C: 45.95%, H: 5.70%, Cl: 6.36, F: 2.69, N: 7.94% found: C: 45.89%, H: 5.54%, Cl: 6.45, F: 2.88, N: 7.91%

bond NHCO bond

CH2CH2 [M + 1]⁺ = 1762 calcd, for C81H92Cl2F3N11O26•1.2HCl•16.9H2O C: 46.07%, H: 6.06%, Cl: 5.37, F: 2.70, N: 7.30% found: C: 46.08%, H: 5.91%, Cl: 5.29, F: 2.24, N: 7.34%

bond CONH bond

CH2 [M + 1]⁺ = 1729 calcd. for C78H84Cl4N12O25•1.7HCl•13.0H2O C: 46.20%, H: 5.55%, Cl: 9.97, N: 8.29% found: C: 46.06%, H: 5.29%, Cl: 9.98, N: 8.21%

bond CONH bond

CH2 [M + 1]⁺ = 1786 calcd. for C81H91Cl4N13O25•2.4HCl•12.5H2O C: 46.30%, H: 5.68%, Cl: 10.80, N: 8.67% found: C: 46.21%, H: 5.63%, Cl: 10.85, N: 8.69%

bond CONH bond

CH2CH2 [M + 1]⁺ = 1747 calcd. for C79H90Cl4N12O25•2.4HCl•15.0H2O C: 45.03%, H: 5.85%, Cl: 10.77, N: 7.98% found: C: 45.14%, H: 5.73%, Cl: 10.75, N: 7.81%

TABLE 92

bond NHCO NH

CH2CH2 [M + 1]⁺ = 1762 calcd. for C79H91Cl4N13O25•2.0HCl•14.0H2O C: 45.41%, H: 5.84%, Cl: 10.18, N: 8.71% found: C: 45.46%, H: 5.80%, Cl: 10.01, N: 8.12%

bond CONH bond

CH2 [M + 1]⁺ = 1719 calcd. for C81H92Cl2N12O26•1.8HCl•16.5H2O C: 46.69%, H: 6.13%, Cl: 6.47, N: 8.07% found: C: 46.84%, H: 5.98%, Cl: 6.52, N: 8.09%

bond CONH bond

CH2 [M + 1]⁺ = 1733 calcd. for C82H94Cl2N12O26•1.7HCl•13.5H2O C: 48.28%, H: 6.06%, Cl: 6.43, N: 8.24% found: C: 48.25%, H: 5.90%, Cl: 6.52, N: 8.08%

bond NHCO bond

CH2CH2 [M + 1]⁺ = 1762 calcd. for C81H92Cl2F3N11O26•1.7HCl•13.0H2O C: 47.23%, H: 5.86%, Cl: 6.37, F: 2.77, N: 7.48% found: C: 47.06%, H: 5.79%, Cl: 6.38, F: 2.78, N: 7.39%

bond NHCO NH

CH2CH2 [M + 1]⁺ = 1777 calcd. for C81H93Cl2F3N12O26•2.5HCl•12.5H2O C: 46.44%, H: 5.80%, Cl: 7.62, F: 2.72, N: 8.02% found: C: 46.30%, H: 5.82%, Cl: 7.63, F: 2.64, N: 7.81%

TABLE 93 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2CH2 [M + 1]⁺ = 1763 calcd. for C80H91Cl2F3N12O26•2.4HCl•13.6H2O C: 45.82%, H: 5.80%, N: 8.02%, Cl: 7.44%, F: 2.72% found: C: 45.47%, H: 5.68%, N: 8.42%, Cl: 7.51%, F: 3.87%

bond NHCO bond

CH2CH2 [M + 1]⁺ = 1763 calcd. for C80H91Cl2F3N12O26•2.7HCl•14.1H2O C: 45.39%, H: 5.80%, N: 7.94%, Cl: 7.87%, F: 2.69% found: C: 45.11%, H: 5.82%, N: 8.00%, Cl: 7.88% F: 2.44%

bond NHCO NH

CH2CH2 [M + 1]⁺ = 1778 calcd. for C80H92Cl2F3N13O26•2.5HCl•15.3H2O C: 44.77%, H: 5.87%, N: 8.48%, Cl: 7.43%, F: 2.66% found: C: 44.56%, H: 5.82%, N: 8.43%, Cl: 7.46%, F: 2.75%

TABLE 94

bond NHCO bond

CH2 [M + 1]⁻ = 1743 calcd. for C80H84Cl2F3N11O26•1.8HCl•13.5H2O C: 46.82%, H: 5.54%, N: 7.51%, Cl: 6.56%, F: 2.78% found: C: 46.80%, H: 5.39%, N: 7.63%, Cl: 6.58% F: 2.71%

bond CONH bond

CH2 [M + 1]⁻ = 1742 [M − Cl]⁻ = 1780 calcd. for C80H84Cl2F3N11O26•2.6HCl•14.5H2O C: 45.77%, H: 5.55%, N: 7.34%, Cl: 7.77% F: 2.71% found: C: 45.77%, H: 5.61%, N: 7.37%, Cl: 7.86%, F: 2.84%

bond NHCO NH

CH2CH2 [M + H]⁺ = 1778 calcd. for C80H92Cl2F3N13O26•0.4HCl•18.3H2O C: 45.24%, H: 6.12%, N: 8.57%, Cl: 4.01% F: 2.68% found: C: 44.88%, H: 5.74%, N: 8.38%, Cl: 3.98% F: 2.72%

bond NHCO NH

CH2CH2 [M + H]⁺ = 1752 calcd. for C82H99Cl2N13O26•2.7HCl•13H2O C: 47.21%, H: 6.17%, N: 8.73%, Cl: 7.99% found: C: 47.09%, H: 6.12%, N: 8.53%, Cl: 8.01%

bond NHCO NH

CH2CH2 [M + H]⁺ = 1766 calcd. for C83H101Cl2N13O26•2.6HCl•13.5H2O C: 47.34%, H: 6.25%, N: 8.65%, Cl: 7.74% found: C: 47.32%, H: 6.11%, N: 8.67%, Cl: 7.69%

TABLE 95

bond CONH bond

CH2CH2 [M + H]⁺ = 1737 calcd. for C82H98Cl2N12O26•2.4HCl•16H2O C: 46.58%, H: 6.31%, N: 7.95%, Cl: 7.38% found: C: 46.69%, H: 6.04%, N: 7.90%, Cl: 7.53%

bond CONH bond

CH2CH2 [M + H]⁺ = 1751 calcd. for C83H100Cl2N12O26•2.4HCl•17H2O C: 46.44%, H: 6.41%, N: 7.83%, Cl: 7.27% found: C: 46.38%, H: 6.12%, N: 7.85%, Cl: 7.33%

bond CONH bond

CH2 [M + 1]⁻ = 1729 calcd. for C84H94Cl2N10O26•1.9HCl•10.8H2O C: 50.59%, H: 5.94%, N: 7.02%, Cl: 6.93% found: C: 50.43%, H: 5.64%, N: 7.15%, Cl: 6.97%

TABLE 96 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) AR2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 1]⁺ = 1745 calcd. for C79H85Cl2F3N12O26•2.0HCl•13.0H2O C: 46.20%, H: 5.55%, Cl: 6.91, F: 2.78, N: 8.18% found: C: 46.25%, H: 5.50%, Cl: 6.46, F: 2.77, N: 8.24%

bond CONH bond

CH2 [M + 1]⁺ = 1749 calcd. for C77H81Cl2F3N12O26S•2.0HCl•14.0H2O C: 44.60%, H: 5.40%, Cl: 6.84, F: 2.75, N: 8.10, S: 1.55% found: C: 44.51%, H: 5.24%, Cl: 7.02, F: 2.42, N: 8.06, S: 1.55%

TABLE 97 R^(A) R^(B) R^(C) R^(D)

OH H H R^(A) Ar2 X3 Y X2 Ar1 X1 Mass Elemental Analysis

bond CONH bond

CH2 [M + 3]⁺ = 1775 [M − 1]⁺ = 1773 calcd. for C82H86Cl2N10O26•2HCl•11H2O C: 48.14%, H: 5.32%, N: 6.84%, Cl: 6.89% found: C: 47.97%, H: 5.09%, N: 6.78%, Cl: 6.68%

bond CONH bond

CH2 [M + 3]⁺ = 1738 [M − 1]⁺ = 1736 calcd. for C81H84Cl2F2N10O27•2HCl•12H2O C: 47.97%, H: 5.36%, N: 6.93%, Cl: 6.99% found: C: 47.87%, H: 4.68%, N: 6.87%, Cl: 6.81%

bond CONH bond

CH2 [M + 3]⁺ = 1786 [M − 1]⁺ = 1784 calcd. for C83H90Cl2F3N11O26•2HCl•12H2O C: 48.06%, H: 5.54%, N: 7.42%, Cl: 6.83% found: C: 47.98%, H: 5.24%, N: 7.44%, Cl: 7.46%

bond CONH bond

CH2 [M + 3]⁺ = 1759 [M − 1]⁺ = 1757 calcd. for C81H85Cl2F3N10O25•2HCl11H2O C: 4792%, H: 5.32%, N: 6.90%, Cl: 6.98% found: C: 47.93%, H: 5.17%, N: 6.90%, Cl: 6.86%

TABLE 98

bond CONH bond

CH2 [M + 3]⁺ =1718 [M + 1]⁻ =1716 calcd. for C83H92Cl2N10O26•2HCl•12H2O C: 49.70%, H: 5.82%, N: 6.98%, Cl: 7.07% found: C: 49.37%, H: 5.47%, N: 7.00%, Cl: 6.57%

bond CONH bond

CH2 [M + 3]⁺ =1731 [M + 1]⁻ =1729 calcd. for C84H94Cl2N10O26•2HCl•14H2O C:49.07%, H: 5.98%, N: 6.81%, Cl: 6.89% found: C: 49.24%, H: 5.91%, N: 6.89%, Cl: 6.59%

bond CONH bond

CH2 [M + 3]⁺ =1731 [M + 1]⁻ =1729 calcd. for C84H94Cl2N10O26•2HCl•10H2O C: 50.85%, H: 5.79%, N: 7.06, Cl: 7.14% found: C: 50.97%, H: 5.86%, N: 7.07%, Cl: 6.79%

bond CONH bond

CH2 [M + 3]⁺ =1749 [M + 1]⁻ =1747 calcd. for C83H92Cl2N10O28•2HCl•14H2O C: 48.05%, H: 5.79%, N: 6.75%, Cl: 6.83% found: C: 47.70%, H: 5.73%, N: 6.79%, Cl: 6.95%

bond CONH bond

CH2 [M + 3]⁺ =1761 [M + 1]⁻ =1759 calcd. for C85H96Cl2N10O27•2HCl•12H2O C: 49.80%, H: 5.90%, N: 6.83%, Cl: 6.91% found: C: 49.82%, H: 5.31%, N: 6.90%, Cl: 7.24%

bond CONH bond

CH2 [M + 3]⁺ =1731 [M + 1]⁻ =1729 calcd. for C84H94Cl2N10O26•2HCl•11H2O C: 50.39%, H: 5.84%, N: 6.99, Cl: 7.08% found: C: 50.28%, H: 5.96%, N: 7.17%, Cl: 6.97%

bond CONH bond

CH2 [M + 3]⁺ =1747 [M + 1]⁻ =1745 calcd. for C84H94Cl2N10O27•2HCl•16H2O C: 48.60%, H: 6.12%, N: 6.74%, Cl: 6.83% found: C: 48.57%, H: 5.82%, N: 7.05%, Cl: 7.05%

TABLE 99 R^(A) R^(B) R^(C) R^(D)

OH or NH—R H or CH2—NH—R H R^(B) R^(C) R^(D) Mass Elemental Analysis

H H [M + 1]⁻ =1907 calcd. for C90H106Cl6N14O24•1.2HCl•9.6H2O C: 49.20%, H: 5.80%, N: 8.92%, Cl: 11.62% found: C: 49.43%, H: 5.75%, N: 7.39%, Cl: 11.62% OH

H [M + 1]⁻ =1768 calcd. for C82H89Cl4N11O25.2•1HCl•8.5H2O C: 49.24%, H: 5.45%, N: 7.70%, Cl: 10.81% found: C: 49.31%, H: 5.54%, N: 7.01%, Cl: 10.77% OH

H [M + 1]⁻ =1933 calcd. for C87H97Cl4N11O31•2.2HCl•10.1H2O C: 47.57%, H: 5.48%, N: 7.01%, Cl: 10.01% found: C: 47.65%, H: 5.50%, N: 6.38%, Cl: 10.07% OH

H [M + 1]⁻ =1937 calcd. for C91H108Cl6N14O25•2.7HCl•14.8H2O C: 46.01%, H: 5.95%, N: 8.25%, Cl: 12.98% found: C: 46.10%, H: 5.87%, N: 7.98%, Cl: 12.90%

TABLE 100 OH

H [M + 1]⁻ =1850 calcd. for C84H91Cl4N15O25•2.0HCl•11.0H2O C: 47.51%, H: 5.46%, N: 9.89%, Cl: 10.02% found: C: 47.59%, H: 5.43%, N: 9.27%, Cl: 10.09%

H H [M + 1]⁻ =1853 calcd. for C86H96Cl4N12O26•2.7HCl•7.4H2O C: 48.17%, H: 5.34%, N: 7.84%, Cl: 11.08% found: C: 48.14%, H: 5.55%, N: 7.88%, Cl: 11.11%

H H [M + 1]⁻ =1854 calcd. for C85H91Cl4N11O28•2.0HCl•8.9H2O C: 48.85%, H: 5.34%, N: 7.37%, Cl: 10.18% found: C: 48.91%, H: 5.24%, N: 7.00%, Cl: 10.25% OH

H [M + 1]⁻ =1884 calcd. for C86H93Cl4N11O29•1.7HCl•10.6H2O C: 48.28%, H: 5.46%, N: 7.20%, Cl: 9.45% found: C: 48.28%, H: 5.40%, N: 7.16%, Cl: 9.41% OH

H [M + 1]⁻ =1976 calcd. for C89H101Cl4N11O32•2.9HCl•11.8H2O C: 46.54%, H: 5.59%, N: 6.71%, Cl: 10.65% found: C: 46.47%, H: 5.17%, N: 6.76%, Cl: 10.59%

H H [M + 3]⁺⁺ =948 calcd. for C89H107Cl6N13O24•2.0HCl•12.7H2O C: 47.36%, H: 6.00%, N: 8.07%, Cl: 12.56% found: C: 47.25%, H: 5.63%, N: 8.24%, Cl: 12.51% OH

H [M + 3]⁺⁺ =958 calcd. for C90H109Cl6N13O25•2.8HCl•14.8H2O C: 45.91%, H: 5.95%, N: 7.73%, Cl: 13.25% found: C: 45.79%, H: 5.52%, N: 8.01%, Cl: 13.20%

TABLE 101 OH

H [M + 3]⁺ = 1872 [M + 1]⁻ = 1870 calcd. for C85H91Cl4N11O29•2.5HCl•12H2O C: 54.52%, H: 4.9%, N: 8.23%, Cl: 7.57% found: C: 46.85%, H: 5.32%, N: 7.08%, Cl: 10.85%

H H [M + 1]⁻ = 1868 calcd. for C87H99Cl4N12O26•3HCl•11H2O C: 55.86%, H: 5.33%, N: 8.99%, Cl: 7.58% found: C: 48.11%, H: 5.62%, N: 7.88%, Cl: 11.09%

H H [M + 3]⁺ = 1856 calcd. for C85H91Cl4N11O29•3HCl•13H2O C: 55.64%, H: 5.27%, N: 9.05%, Cl: 7.64% found: C: 47.21%, H: 5.54%, N: 7.71%, Cl: 11.02%

H H [M + 1]⁻ = 1821 calcd. for C85H91Cl4N11O29•2HCl•14H2O C: 55.33%, H: 4.86%, N: 9.22%, Cl: 7.78% found: C: 47.17%, H: 5.41%, N: 7.91%, Cl: 9.64% OH

H [M + 3]⁺ = 1827 calcd. for C85H96Cl4N12O25•4.5HCl•14.7H2O C: 45.24%, H: 5.80%, N: 7.45%, Cl: 13.36% found: C: 45.15%, H: 5.79%, N: 7.81%, Cl: 13.41% OH

H [M + 3]⁺ = 1870 [M + 1]⁻ = 1868 calcd. for C87H98Cl4N12O26•3.4HCl•14.4H2O C: 46.38%, H: 5.82%, N: 7.46%, Cl: 11.64% found: C: 46.31%, H: 5.56%, N: 7.54%, Cl: 11.68%

H H [M + 3]⁺ = 1839 calcd. for C86H96Cl4N12O25•2.9HCl•14.1H2O C: 46.97%, H: 5.82%, N: 7.64%, Cl: 11.12% found: C: 46.94%, H: 5.70%, N: 7.62%, Cl: 11.10%

TABLE 102

H H [M + 1]⁻ = 1795 calcd. for C84H94Cl4N12O242•7HCl•13.4H2O C: 47.20%, H: 5.82%, N: 7.86%, Cl: 11.11% found: C: 46.17%, H: 5.66%, N: 7.91%, Cl: 11.07%

H H [M + 1]⁻ = 1823 calcd. for C86H99Cl4N12O24•2.6HCl•13.1H2O C: 47.88%, H: 5.97%, N: 7.79%, Cl: 10.85% found: C: 46.87%, H: 5.84%, N: 7.60%, Cl: 10.86%

TABLE 103 R^(A) R^(B) R^(C) R^(D)

OH or NH—R H or CH2—NH—R H R^(B) R^(C) R^(D) Mass Elemental Analysis —NH(CH₂)₂SO₃H H H [M + 3]⁺ = 1850 [M + 1]⁻ = 1848 calcd for C83H90Cl2F3N11O28S•1.2HCl•10.7H2O C: 47.79%, H: 5.44%, N: 7.39%, Cl: 5.44%, F: 2.73%, S: 1.54% found: C: 47.78%, H: 5.23%, N: 7.32%, Cl: 5.37%, F: 2.88%, S: 1.25%

H H [M + 1]⁻ = 1857 calcd. for C85H90Cl2F3N11O29•1.8HCl•12.1H2O C: 47.68%, H: 5.46%, N: 7.20%, Cl: 6.29%, F: 2.66% found: C: 47.67%, H: 5.43%, N: 7.31%, Cl: 6.29%, F: 2.66% —NH(CH₂)₂NHSO₂NH₂ H H [M + 1]⁻ = 1863 calcd. for C83H92Cl2F3N13O27S•2.0HCl•11.0H2O C: 46.70%, H: 5.48%, N: 8.53%, Cl: 6.64%, F: 2.67%, S: 1.50% found: C: 46.76%, H: 5.46%, N: 8.42%, Cl: 6.57%, F: 2.61%, S: 1.33% —NH(CH₂)₂O(CH₂)₂OH H H [M + 3]⁺ = 1831 [M + 1]⁻ = 1829 calcd. for C85H94Cl2F3N11O27•1.9HCl•10.9H2O C: 48.72%, H: 5.66%, N: 7.35%, Cl: 6.60%, F: 2.72% found: C: 48.66%, H: 5.43%, N: 7.41%, Cl: 6.56%, F: 2.66%

TABLE 104

H H [M + 1]⁻ = 1855 calcd. for C85H91Cl2F3N12O28•2.0HCl•12.3H2O C: 47.46%, H: 5.51%, N: 7.81%, Cl: 6.59%, F: 2.65% found: C: 47.44%, H: 5.29%, N: 7.75%, Cl: 6.51%, F: 2.62%

H H [M + 1]⁻ = 1869 calcd. for C87H98Cl2F3N13O26•2.9HCl•13.0H2O C: 47.68%, H: 5.74%, N: 8.31%, Cl: 7.93%, F: 2.60% found: C: 47.57%, H: 5.53%, N: 8.57%, Cl: 7.94%, F: 2.54% OH

H [M + 1]⁻ = 1885 calcd. for C86H93Cl2F3N12O29•1.7HCl•11.5H2O C: 47.91%, H: 5.50%, N: 7.80%, Cl: 6.08%, F: 2.64% found: C: 47.96%, H: 5.36%, N: 7.83%, Cl: 6.00%, F: 2.55% OH

H [M + 3]⁺ = 1844 [M + 1]⁻ = 1842 calcd. for C85H92Cl2F3N11O28•2.1HCl•11.1H2O C: 48.15%, H: 5.53%, N: 7.27%, Cl: 6.86%, F: 2.69% found: C: 48.10%, H: 5.36%, N: 7.42%, Cl: 6.86%, F: 2.57% OH

H [M + 1]⁻ = 1878 calcd. for C84H92Cl2F3N11O29S•1.2HCl•12.0H2O C: 47.15%, H: 5.52%, N: 7.20%, Cl: 5.30%, F: 2.66%, S: 1.50% found: C: 47.14%, H: 5.29%, N: 7.24%, Cl: 5.42%, F: 2.60%, S: 1.37% OH

H [M + 1]⁻ = 1865 calcd. for C83H91Cl2F3N11O29P•1.6HCl•12.4H2O C: 46.43%, H: 5.51%, N: 7.18%, Cl: 5.94%, F: 2.65%, P: 1.44% found: C: 46.42%, H: 5.34%, N: 7.16%, Cl: 6.00%, F: 2.58%, P: 1.60%

TABLE 105 OH

H [M + 1]⁻ = 1892 calcd. for C84H94Cl2F3N13O28S•2.0HCl•12.6H2O C: 45.99%, H: 5.57%, N: 8.30%, Cl: 6.46% F: 2.60%, S: 1.46% found: C: 45.75%, H: 5.49%, N: 8.60%, Cl: 6.53%, F: 2.57%, S: 1.68% OH

H [M + 3]⁺ = 2030 calcd. for C94H111Cl2F3N14O29•3.0HCl•12.9H2O.02CF3COOH C: 47.37%, H: 5.90%, N: 8.19%, Cl: 7.41% F: 2.86% found: C: 47.40%, H: 5.91%, N: 8.15%, Cl: 7.50%, F: 2.96% OH

H [M + 3]⁺ = 2058 calcd. for C94H111Cl2F3N16O29•2.7HCl•12.8H2O.07CF3COOH C: 46.47%, H: 5.72%, N: 9.09%, Cl: 6.76% F: 3.93% found: C: 46.49%, H: 5.71%, N: 9.06%, Cl: 6.75%, F: 3.95% OH

H [M + 1]⁻ = 1858 calcd. for C86H96Cl2F3N11O28•2.3HCl•11.9H2O C: 47.87%, H: 5.70%, N: 7.14%, Cl: 7.06% F: 2.64% found: C: 47.82%, H: 5.60%, N: 7.21%, Cl: 7.03%, F: 2.55%

H H [M + 1]⁻ = 1813 calcd. for C84H90Cl2F3N11O27•1.8HCl•10.4H2O C: 48.82%, H: 5.49%, N: 7.46%, Cl: 6.52% F: 2.76% found: C: 48.77%, H: 4.53%, N: 7.14%, Cl: 6.59%, F: 2.61%

H H [M + 3]⁺ = 1827 [M + 1]⁻ = 1825 calcd. for C86H97Cl2F3N12O25•2.9HCl•12.4H2O C: 47.91%, H: 5.83%, N: 7.80%, Cl: 8.06% F: 2.64% found: C: 47.89%, H: 5.60%, N: 8.01%, Cl: 8.01%, F: 2.72%

TABLE 106

H H [M + 3]⁺ = 1827 [M + 1]⁻ = 1825 calcd. for C86H98Cl3F3N12O25•1.9HCl•13.3H2O C: 47.56%, H: 5.87%, N: 7.74%, Cl: 8.00% F: 2.62% found: C:47.54%, H: 5.69%, N: 7.87%, Cl: 8.06% F: 2.55%

H H [M + 1]⁻ = 1892 calcd. for C88H94Cl2F3N13O27•3.0HCl•14.1H2O C: 46.83%, H: 5.59%, N: 8.01%, Cl: 7.85% F: 2.53% found: C: 46.78%, H: 5.51%, N: 8.13%, Cl: 7:18% F: 2.51%

H H [M + 1]⁻ = 1955 calcd. for C89H103Cl2F3N16O25S•1.9HCl•14.5H2O C: 46.02%, H: 5.81%, N: 9.65%, Cl: 7.48% F: 2.45%, S: 1.38% found: C: 45.97%, H: 5.66%, N: 9.77%, Cl: 7.49% F: 2.48%, S: 1.35%

H H [M + 1]⁻ = 1828 calcd. for C85H94Cl2F3N11O27•2.1HCl•11.9H2O C: 48.14%, H: 5.70%, N: 7.27%, Cl: 6.85% F: 2.69% found: C: 47.13%, H: 5.66%, N: 7.25%, Cl: 6.81% F: 2.72%

H H [M + 1]⁻ = 1878 calcd. for C87H92Cl2F3N13O27•2.8HCl•14.4H2O C: 46.62%, H: 5.56%, N: 8.12%, Cl: 7.59% F: 2.54% found: C: 46.65%, H: 5.48%, N: 7.96%, Cl: 7.58% F: 2.49%

H H [M + 1]⁻ = 1853 calcd. for C87H97Cl2F3N12O26•2.8HCl•15.0H2O C: 46.92%, H: 5.87%, N: 7.55%, Cl: 7.64% F: 2.56% found: C: 46.89%, H: 5.65%, N: 7.55%, Cl: 7.64% F: 2.46%

TABLE 107

H H [M + 3]⁺ = 1830 [M + 1]⁻ = 1828 calcd. for C85H94Cl2F3N11O27•2.9HCl•11.8H2O C: 47.53%, H: 5.65%, N: 7.17%, Cl: 8.09% F: 2.65% found: C: 47.46%, H: 5.49%, N: 7.21%, Cl: 8.13% F: 2.64%

TABLE 108 R^(A) R^(B) R^(C) R^(D)

OH or NH—R H or CH2—NH—R H R^(B) R^(C) R^(D) Mass Elemental Analysis —NH(CH₂)₂O(CH₂)₂OH H H [M + 3]⁺ = 1847 calcd. for C83H93Cl4N132O27•2.3HCl•13.5H2O C: 45.86%, H: 5.67%, N: 8.38%, Cl: 10.28% found: C: 45.80%, H: 5.45%, N: 8.50%, Cl: 10.26% —NH(CH₂)₂NHSO₂NH₂ H H [M + 3]⁺ = 1881 calcd. for C81H91Cl4N15O27S•2.1HCl•11.1H2O C: 45.10%, H: 5.39%, N: 9.74%, Cl: 10.03%, S: 1.49% found: C: 45.16%, H: 5.36%, N: 9.54%, Cl: 9.98%, S: 1.28% —NHCH₂CONHCN H H [M + 3]⁺ = 1841 calcd. for C82H87Cl4N15O26•2.5HCl•12.9H2O C: 45.51%, H: 5.37%, N: 9.71%, Cl: 10.65% found: C: 45.50%, H: 5.36%, N: 9.73%, Cl: 10.67% —NH(CH₂)₂OMe H H [M + 3]⁺ = 1817 calcd. for C82H91Cl4N13O26•1.8HCl•11.8H2O C: 47.02%, H: 5.60%, N: 8.69%, Cl: 9.82% found: C: 47.04%, H: 5.54%, N: 8.64%, Cl: 9.85% —NHCH₂CONH2 H H [M + 3]⁺ = 1816 calcd. for C81H88Cl4N14O26•2.0HCl•11.9H2O C: 46.27%, H: 5.45%, N: 9.33%, Cl: 10.12% found: C: 46.27%, H: 5.34%, N: 9.38%, Cl: 10.16%

TABLE 109 R^(A) R^(B) R^(C) R^(D)

OH or NH—R H or CH2—NH—R H R^(B) R^(C) R^(D) Mass Elemental Analysis

H H [M + 1]⁻ = 1864 calcd. for C82H91Cl2F3N14O27S•2.2HCl•14.3H2O C: 44.72%, H: 5.57%, N: 8.90%, Cl: 6.76%, F: 2.59%, S: 1.46% found: C: 44.67, H: 5.38%, N: 8.99%, Cl: 6.79%, F: 2.70%, S: 1.51%

TABLE 110 R^(A) R^(B) R^(C) N-terminal

OH or NH—R H or CH2—NH—R

R^(B) R^(C) N-terminal Mass Elemental Analysis OH H

[M + 3]⁺ = 1687 [M + 1]⁻ = 1685 calcd. for C77H77Cl2F3N10O26•1.8HCl•13.6H2O C: 46.31%, H: 5.33%, N: 7.01%, Cl: 6.75%, F: 2.85% found: C: 46.34%, H: 5.42%, N: 6.95%, Cl: 6.79%, F: 2.66% OH H

[M + 1]⁻ = 1711 calcd. for C79H79Cl2F3N10O26•1.4HCl•14.4H2O C: 46.91%, H: 5.44%, N: 6.92%, Cl: 5.96%, F: 2.82% found: C: 46.86%, H: 5.32%, N: 6.84%, Cl: 5.99%, F: 2.93%

TABLE 111 OH H

[M + 1]⁻ = 1743 calcd. for C80H84Cl2F3N11O26•2.6HCl•15.2H2O C: 45.49%, H: 5.58%, N: 7.29%, Cl: 7.72%, F: 2.70% found: C: 45.53%, H: 5.52%, N: 7.07%, Cl: 7.77%, F: 2.56% OH H

[M + 1]⁻ = 1751 calcd. for C80H79Cl2F3N12O26•2.7HCl•15.7H2O C: 45.03%, H: 5.34%, N: 7.88%, Cl: 7.81%, F: 2.67% found: C: 44.99%, H: 5.17%, N: 7.99%, Cl: 7.77%, F: 2.66%

Example 13

The following compounds were prepared in a similar manner as described above. TABLE 112 Structure Mass Elemental Analysis

[M + H]⁺ = 1695 calcd. for C81H80Cl2N10O27 2.9(HCl) 15(H2O) C: 46.94%, H: 5.49%, Cl: 8.38%, N: 6.76%, O: 32.42% found: C: 47.04%, H: 4.92%, Cl: 8.25%, N: 6.95%

[M + 1]⁺ = 1878 calcd. for C91H101Cl2N13C27•3.5HCl•12H2O C: 49.15%, H: 5.82%, N: 8.19%, Cl: 8.77%, C: 28.06%, found: C: 49.05%, H: 5.69%, N: 8.30%, Cl: 8.61%

[M + 1]⁺ = 1811 calcd. for C85H95Cl2F3N12O25•3.5HCl•16H2O C: 45.81%, H: 5.90%, N: 7.54%, Cl: 8.75%, F: 2.56%, O29.44% found: C: 45.64%, H: 5.64%, N: 7.51%, Cl: 8.72%, F: 2.04%

TABLE 113 Structure Mass Elemental Analysis

[M + 1]⁺ =1800 calcd. for C83H90Cl2F3N11O27•1.9HCl•13H2O C: 47.36%, H: 5.65%, N: 7.32%, Cl: 6.57%, F: 2.71%, O: 30.40%, found: C: 47.48%, H: 5.55%, N: 7.44%, Cl: 6.49%, F: 2.74%

[M + 1]⁺ =1768 calcd. for C83H90Cl2F3N11O25•2.1HCl•13H2O C: 47.92%, H: 5.72%, N: 7.41%, Cl: 6.99%, F 2.74%, O29.23%, found: C: 47.82%, H: 5.74%: N: 7.53%, Cl: 7.24%, F: 2.96%

[M + 1]⁺ =1741 calcd. for C81H85Cl2F3N10O26•1.5HCl•11H2O C: 48.76%, H: 5.48%, N: 7.02%, Cl: 6.22%, F: 2.86%, O: 29.67%, found: C: 48.55%, H: 5.58%, N: 7.03%, Cl: 6.20%, F: 2.91%

[M + 1]⁺ =1695 calcd. for C81H80Cl2N10O27•2HCl•12H2O C: 49.0%, H: 5.38%, N: 7.05%, Cl: 7.14%, C: 31.43%, found: C: 49.16%, H: 5.24%, N: 7.18%, Cl: 7.0%

Example 14

The following compounds were prepared in a similar manner as described above. TABLE 114 Structure Mass Elemental Analysis

[M + 1]⁺ = 1921 calcd. for C90H95Cl2F3N12O28•3.3HCl•13.8H2O C: 47.21%, H: 5.54%, N: 7.34%, Cl: 8.21%, F: 2.49% found: C: 47.17%, H: 5.40%, N: 7.53%, Cl: 8.18%, F: 2.65%

[M + 1]⁺ = 1723 calcd. for C80H90Cl2N12O25S1•1.6HCl•13.2H2O C: 47.60%, H: 5.89%, N: 8.33%, Cl: 6.32%, S: 1.59% found: C: 47.62%, H: 5.80%, N: 8.27%, Cl: 6.29%, S: 1.64%

[M + 1]⁺ = 1732 calcd. for C83H93Cl2N11O26•1.0HCl•13.8H2O C: 49.43%, H: 6.08%, N: 7.64%, Cl: 5.27% found: C: 49.47%, H: 6.01%, N: 7.65%, Cl: 4.98%

TABLE 115

[M + 1]⁺ = 1729 calcd. for C79H83Cl4N11O25•1.4HCl•11.4H2O C: 47.81%, H: 5.44%, N: 7.76%, Cl: 9.65% found: C: 47.78%, H: 5.33%, N: 7.75%, Cl: 9.67%

[M + 1]⁺ = 1758 calcd. for C81H86Cl2F3N11O26•1.9HCl•12.4H2O C: 47.45%, H: 5.54%, N: 7.52%, Cl: 6.74%, F: 2.78 found: C: 47.43%, H: 5.46%, N: 7.56%, Cl: 6.75%, F: 2.83

[M + 1]⁺ = 1785 calcd. for C87H100Cl2N12O25•2.8HCl•11.5H2O C: 49.90%, H: 6.06%, N: 8.03%, Cl: 8.13% found: C: 49.87%, H: 6.00%, N: 8.15%, Cl: 8.14%

TABLE 116

[M + 1]⁺ = 1823 calcd. for C86H95Cl2F3N12O25•1.6HCl•11.3H2O C: 49.50%, H: 5.76%, N: 8.06%, Cl: 6.12%, F: 2.73% found: C: 49.47%, H: 5.74%, N: 8.13%, Cl: 6.16%, F: 2.66%

[M + 1]⁺ = 1756 calcd. for C81H86Cl2F3N11O26•2.6HCl•9.9H2O C: 47.91%, H: 5.38%, N: 7.59%, Cl: 8.03%, F: 2.81% found: C: 47.87%, H: 5.32%, N: 7.67%, Cl: 7.96%, F: 2.86%

[M + 1]⁺ = 1788 calcd. for C80H86Cl2F3N13O27•2.2HCl•9.8H2O C: 46.96%, H: 5.31%, N: 8.90%, Cl: 7.28, F: 2.79% found: C: 46.93%, H: 5.30%, N: 9.02%, Cl: 7.33, F: 2.79%

TABLE 117

[M + 1]⁺ = 1799 calcd. for C82H87Cl2F3N12O27•1.4HCl•9.4H2O C: 48.73%, H: 5.35%, N: 8.32%, Cl: 5.96, F: 2.82% found: C: 46.69%, H: 5.31%, N: 8.48%, Cl: 6.01, F: 2.76%

[M + 1]⁺ = 1749 calcd. for C81H87Cl3N12O26•1.2HCl•11.2H2O C: 48.73%, H: 5.58%, N: 8.42%, Cl: 7.46% found: C: 48.68%, H: 5.49%, N: 8.50%, Cl: 7.403%

[M + 1]⁺ = 1760 calcd. for C83H95Cl2N13O26•1.2HCl•11.7H2O C: 49.45%, H: 5.98%, N: 9.03%, Cl: 5.63% found: C: 49.44%, H: 5.86%, N: 9.04%, Cl: 5.64%

TABLE 118

[M + 1]⁺ = 1805 calcd. for C81H86Cl2F4N12O27•1.7HCl•10.4H2O C: 47.32%, H: 5.32%, N: 8.18%, Cl: 6.38%, F: 3.70% found: C: 47.33%, H: 5.36%, N: 8.30%, Cl: 6.35%, F: 3.70%

[M + 1]⁺ = 1789 calcd. for C80H85Cl2F3N12O26S•1.7HCl•10.3H2O C: 47.14%, H: 5.31%, N: 8.25%, Cl: 6.44%, F: 2.80%, S: 1.57% found: C: 47.10%, H: 5.26%, N: 8.32%, Cl: 6.48%, F: 2.88%, S: 1.53%

[M + 1]⁺ = 1762 calcd. for C81H89Cl2N13O28•1.4HCl•13.4H2O C: 47.32%, H: 5.75%, N: 8.86%, Cl: 5.86% found: C: 47.30%, H: 5.70%, N: 9.03%, Cl: 5.88%

TABLE 119

[M + 1]⁺ = 1741 calcd. for C79H84Cl3FN12O26•1.4HCl•13.1H2O C: 46.74%, H: 5.54%, N: 8.28%, Cl: 7.68%, F: 0.94% found: C: 46.72%, H: 5.26%, N: 8.34%, Cl: 7.70%, F: 1.04%

[M + 1]⁺ = 1771 calcd. for C80H86Cl2F2N12O26S•1.5HCl•10.9H2O C: 47.48%, H: 5.44%, N: 8.31%, Cl: 6.13%, F: 1.88%, S: 1.58% found: C: 47.48%, H: 5.31%, N: 8.35%, Cl: 6.19%, F: 1.96%, S: 1.59%

[M + 1]⁺ = 1710 calcd. for C80H94Cl2N12O26•1.5HCl•13.0H2O C: 48.94%, H: 6.03%, N: 8.56%, Cl: 6.32% found: C: 48.89%, H: 5.91%, N: 8.63%, Cl: 6.33%

TABLE 120

[M + 1]⁺ = 1751 calcd. for C83H100Cl2N12O26•1.5HCl•12.4H2O C: 49.09%, H: 6.27%, N: 8.28%, Cl: 6.11% found: C: 49.04%, H: 6.21%, N: 8.44%, Cl: 6.06%

[M + 1]⁺ = 1775 calcd. for C84H96Cl2N12O27•1.5HCl•11.8H2O C: 49.36%, H: 5.97%, N: 8.22%, Cl: 6.07% found: C: 49.31%, H: 5.77%, N: 8.34%, Cl: 6.02%

[M + 1]⁺ = 1787 calcd. for C81H87Cl2F3N12O27•1.6HCl•10.2H2O C: 47.91%, H: 5.41%, N: 8.28%, Cl: 6.29%, F: 2.81% found: C: 47.87%, H: 5.33%, N: 8.35%, Cl: 6.27%, F: 2.90%

TABLE 121

[M + 1]⁺ = 1760 calcd. for C79H86Cl2F3N13O26•2.0HCl•12.0H2O C: 46.27%, H: 5.51% N: 8.88%, Cl: 6.92%, F: 2.78% found: C: 46.41%, H: 5.51%, N: 8.43%, Cl: 6.85%, F: 2.96%

[M + 1]⁺ = 1760 calcd. for C81H90Cl2F3N11O26•2.0HCl•10.0H2O C: 48.29%, H: 5.60%, N: 7.65%, Cl: 7.04%, F: 2.83% found: C: 48.33%, H: 5.63%, N: 7.51%, Cl: 7.00%, F: 3.08%

[M + 1]⁺ = 1778 calcd. for C81H92Cl2F3N11O27•1.9HCl•10.5H2O C: 47.74%, H: 5.68%, N: 7.56%, Cl: 6.78%, F: 2.80% found: C: 47.73%, H: 5.58%, N: 7.63%, Cl: 6.71%, F: 2.74%

TABLE 122

[M + 1]⁺ = 1777 calcd. for C81H93Cl2F3N12O26•2.8HCl•11.5H2O C: 46.60%, H: 5.74%, N: 8.05%, Cl: 8.15%, F: 2.73% found: C: 46.61%, H: 5.59%, N: 7.80%, Cl: 8.09%, F: 2.44%

[M + H]⁺ = 1750 calcd. for C79H88Cl2F3N11O27•1.8HCl•12.2H2O C: 46.58%, H: 5.65%, N: 7.56%, Cl: 6.61%, F: 2.80% found: C: 46.41%, H: 5.48%, N: 7.71%, Cl: 6.65%, F: 2.77%

[M + H]⁺ = 1807 calcd. for C82H95Cl2F3N12O27•3.1HCl•11.2H2O C: 46.38%, H: 5.72%, N: 7.92%, Cl: 8.52%, F: 2.68% found: C: 46.24%, H: 5.66%, N: 7.95%, Cl: 8.62%, F: 2.82%

TABLE 123

[M + 1]⁺ = 1765

[M + 1]⁻ = 1855 calcd. for C86H95Cl2F3N12O27•1.5HCl•9.2H2O C: 49.73%, H: 5.58%, N: 8.09%, Cl: 5.97%, F: 2.74% found: C: 49.71%, H: 5.58%, N: 8.18%, Cl: 5.95%, F: 2.80%

[M + 1]⁻ = 1839 calcd. for C85H94Cl4N12O26•1.8HCl•11.2H2O C: 48.41%, H: 5.65%, N: 7.97%, Cl: 9.75% found: C: 48.41%, H: 5.66%, N: 8.07%, Cl: 9.71%

TABLE 124 Structure Mass Elemental Analysis

[M + 1]⁺ = 1784 calcd. for C82H90Cl2F3N13O25•2.4HCl•1.0H2O C: 47.97%, H: 5.52%, N: 8.87%, Cl: 7.60%, F: 2.78% found: C: 47.98%, H: 5.39%, N: 8.98%, Cl: 7.61%, F: 2.82%

[M + 1]⁺ = 1809 calcd. for C83H89Cl2F3N14O25•2.3HCl•10.7H2O C: 47.76%, H: 5.44%, N: 9.40%, Cl: 7.30%, F: 2.73% found: C: 47.75%, H: 5.24%, N: 9.41%, Cl: 7.29%, F: 2.77%

[M + 1]⁺ = 1784 calcd. for C82H90Cl2F3N13O25•2.3HCl•10.7H2O C: 47.84%, H: 5.53%, N: 8.85%, Cl: 7.58%, F: 2.77% found: C: 47.80%, H: 5.45%, N: 8.92%, Cl: 7.53%, F: 2.87%

TABLE 125

[M + 1]⁺ = 1800 calcd. for C82H90Cl2F3N13O26•2.3HCl•10.5H2O C: 47.47%, H: 5.50%, N: 8.78%, Cl: 7.35%, F: 2.75% found: C: 47.46%, H: 5.40%, N: 8.88%, Cl: 7.37%, F: 2.68%

[M + 1]⁺ = 1830 calcd. for C82H91Cl4N13O27•1.9HCl•10.3H2O C: 47.18%, H: 5.48%, N: 8.72%, Cl: 10.02% found: C: 47.14%, H: 5.38%, N: 8.82%, Cl: 10.06%

[M + 1]⁺ = 1844 calcd. for C82H90Cl2F3N15O27•2.2HCl•7.2H2O C: 47.91%, H: 5.23%, N: 10.22%, Cl: 7.24, F: 2.77% found: C: 47.94%, H: 5.25%, N: 10.05%, Cl: 7.28, F: 2.65%

TABLE 126

[M + 1]⁺ = 1843 calcd. for C83H91Cl2F3N14O27•2.2HCl•10.0H2O C: 47.36%, H: 5.42%, N: 9.32%, Cl: 7.07, F: 2.71% found: C: 47.32%, H: 5.36%, N: 9.34%, Cl: 7.11, F: 2.78%

[M + 1]⁺ = 1885 calcd. for C85H96Cl4N14O27•2.7HCl•9.9H2O C: 47.17%, H: 5.52%, N: 9.06%, Cl: 10.97% found: C: 47.16%, H: 5.43%, N: 9.10%, Cl: 10.96%

[M + 1]⁺ = 1844 calcd. for C83H93Cl4N13O27•1.7HCl•9.9H2O found: C: 47.77%, H: 5.53%, N: 8.73%, Cl: 9.68% C: 47.75%, H: 5.35%, N: 8.74%, Cl: 9.74%

TABLE 127 Structure Mass Elemental Analysis

[M + 1]⁺ =1891 calcd. for C87H94Cl4N14O26•4.2HCl•11.6H2O C: 46.32%, H: 5.42%, N: 8.69%, Cl: 12.89% found: C: 46.32%, H: 5.28%, N: 8.81%, Cl: 12.83%

Reference Example

The following compounds were prepared in a similar manner as described above. TABLE 128 Structure Mass Elemental Analysis

[M + 1]⁺ = 1562 calcd. for C73H73Cl2N9O26•2HCl•10H2O C: 48.27%, H: 5.27%, N: 6.94%, Cl: 7.81%, O: 31.71% found: C: 48.02%, H: 5.05%, N: 7.01%, Cl: 7.81%

[M + 1]⁺ = 1821 calcd. for C88H94Cl2N12O27•2HCl•14H2O C: 49.21%, H: 5.82%, N: 7.83%, Cl: 6.60%, O: 30.54%, found: C: 49.21%, H: 6.03%, N: 7.90%, Cl: 6.75%

Test Example 1

In vitro assay of antimicrobial activity

Method

For several compounds of the invention, minimal inhibitory concentration (MIC) was determined by the microdilution method using cation adjusted Mueller-Hinton broth well known in the art.

Results

The compounds of the invention showed a strong antimicrobial activity against various bacteria, including vancomycin-resistant strains. In particular, as shown in the following table, the compound of the invention, showed notability stronger antimicrobial activity against vancomycin-resistant enterococcus (VRE VanA) than existing drugs. TABLE 129 Compound Compound Compound 6 10 16 Strain No. (Example 1) (Example 2) (Example 4) VCM TEIC E. faecalis 4 2 4 >64 >64 SR7914 (VRE: Van A) E. faecium 4 2 4 >64 >64 SR7917 (VRE: Van A)

VCM and TEIC mean vancomycin and teicoplanin, respectively.

Formulations

It is to be noted that the following Formulations 1 to 8 are mere illustration, but not intended to limit the scope of the invention. The term “active ingredient” means the compounds of the invention, a tautomer, a prodrug, a pharmaceutically acceptable salt or a solvate thereof.

Formulation 1

Hard gelatin capsules are prepared using of the following ingredients: Dose (mg/capsule) Active ingredient 250 Starch, dried 200 Magnesium stearate 10 Total 460 mg

Formulation 2

A tablet is prepared using of the following ingredients: Dose (mg/tablet) Active ingredient 250 Cellulose, microcrystals 400 Silicon dioxide, fumed 10 Stearic acid 5 Total 665 mg

The components are blended and compressed to form tablets each weighing 665 mg.

Formulation 3

An aerosol solution is prepared containing the following components: Weight Active ingredient 0.25 Ethanol 25.75 Propellant 22 (chlorodifluoromethane) 74.00 Total 100.00

The active compound is mixed with ethanol and the admixture added to a portion of the propellant 22, cooled to −30° C. and transferred to filling device. The required amount is then fed to stainless steel container and diluted with the reminder of the propellant. The valve units are then fitted to the container.

Formulation 4

Table ts, each containing 60 mg of active ingredient, are made as follows. Active ingredient 60 mg Starch 45 mg Microcrystals cellulose 35 mg Polyvinylpyrrolidone 4 mg (as 10% solution in water) Sodium carboxymethyl starch 4.5 mg Magnesium stearate 0.5 mg Talc 1 mg Total 150 mg

The active ingredient, starch, and cellulose are passed through a No. 45 mesh U.S. sieve, and the mixed thoroughly. The aqueous solution containing polyvinylpyrrolidone is mixed with the resultant powder, and the admixture then is passed through a No. 14 mesh U.S. sieve. The granules so produced are dried at 50° C. and passed through a No. 18 mesh U.S. sieve. The sodium carboxymethyl starch, magnesium stearate, and talc, previously passed through No. 60 mesh U.S. sieve, are then added to the granules which, after mixing, are compressed on a tablet machine to yield tablets each weighing 150 mg.

Formulation 5

Capsules, each containing 80 mg of active ingredient, are made as follows: Active ingredient 80 mg Starch 59 mg Microcrystals cellulose 59 mg Magnesium stearate 2 mg Total 200 mg

The active ingredient, cellulose, starch, and magnesium stearate are blended, passed through a No. 45 mesh U.S. sieve, and filled into hard gelatin capsules in 200 mg quantities.

Formulation 6

Suppository, each containing 225 mg of active ingredient, are made as follows: Active ingredient 225 mg Saturated fatty acid glycerides 2000 mg Total 2225 mg

The active ingredient is passed through a No. 60 mesh U.S. sieve and suspended in the saturated fatty acid glycerides previously melted using the minimum heat necessary. The mixture is then poured into a suppository mold of nominal 2 g capacity and allowed to cool.

Formulation 7

Suspensions, each containing 50 mg of active ingredient per 5 ml dose, are made as follows: Active ingredient 50 mg Sodium carboxymethyl cellulose 50 mg Syrup 1.25 mL Benzoic acid solution 0.10 mL Flavor q.v. Color q.v. Purified water to total 5 mL

The active ingredient is passed through a No. 45 U.S. sieve, and mixed with the sodium carboxymethyl cellulose and syrup to form a smooth paste. The benzoic acid solution, flavor and color are diluted with a portion of the water and added, with stirring. Sufficient water is then added to produce the required volume.

Formulation 8

An intravenous formulation may be prepared as follows: Active ingredient 100 mg Isotonic saline 1000 mL

The solution of the above ingredients generally is administered intravenously to a subject at a rate of 1 mL per minute.

INDUSTRIAL APPLICABILITY

The glycopeptide derivatives of the invention, pharmaceutically acceptable salts and solvates thereof are useful in the medical treatment and show a biological activity, including antimicrobial activity. Accordingly, the present invention provides a method for the treatment of infections diseases, particularly diseases caused by gram-positive microbial in animal, and the compounds of the invention is particularly useful in the treatment of infections with methicillin resistant staphylococcus. The compound is also useful for the treatment of infections with enterococcus including vancomycin-resistant enterococcus (VRE). Example of such disease includes severe infections with staphylococcus such as staphylococcal endocarditis and staphylococcal sepsis. 

1. A compound of the formula: (aglycon part of glycopeptide antibiotic derivative)-(Sac-NH)—R^(A), or a pharmaceutically acceptable salt or solvate thereof, wherein, (aglycon part of glycopeptide antibiotic derivative) is a part of known glycopeptide antibiotic derivative from which a sugar moiety have been removed: (Sac-NH) is an amino sugar or an amino sugar-containing sugar chain; R^(A) is presented by the formula: —X¹—Ar¹—X²—Y—X³—Ar² wherein X¹, X² and X³ are independently 1) single bond; 2) a heteroatom-containing group selected from the group consisting of —N═, ═N—, —NR¹— wherein R₁ is hydrogen or lower alkyl, —O—, —S—, —SO— and —SO₂—, or a linkage thereof; or 3) optionally substituted alkylene or alkenylene optionally interrupted by one or more same or different heteroatomic group; Y is —NR²CO—, —CONR²— wherein R² is hydrogen or lower alkyl, or a group of the formula:

wherein R³ is alkylene; and Ar¹ and Ar² are independently a carbocycle or heterocycle which is optionally substituted and may have an unsaturated bond, with the proviso that (aglycon part of glycopeptide antibiotic derivative)-(Sac-NH) moiety is not a group of the formula:

wherein R is sugar residue.
 2. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein (Sac-NH) moiety is L-vancosaminyl, 3-desmethyl-vancosaminyl, 3-epi-vancosaminyl, 4-keto-vancosaminyl, acosaminyl, actinosaminyl, daunosaminyl, 3-epi-daunosaminyl, ristosaminyl, N-methyl-D-glucaminyl, N-Acetyl-D-glucosamyl, or N-acyl-D-glucosamyl.
 3. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein (Sac-NH) moiety is L-vancosaminyl.
 4. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, excluding that R^(A) is 4-(monofluorobenzoylamino)benzyl.
 5. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, excluding that Ar¹ is phenylene; Y is —NR²CO—; and Ar² is monofluorophenyl.
 6. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, excluding that Ar² is, monofluorophenyl.
 7. The compound according to claim 1 represented by the formula:

a pharmaceutically acceptable salt or solvate thereof, wherein, R^(A) is formula: —X¹—Ar¹—X²—Y—X³—Ar² wherein, X¹, X² and X³ are independently, 1) single bond, 2)-N═, ═N—, —NR¹— (wherein R¹ is hydrogen or lower alkyl), —O—, —S—, —SO— and —SO₂— selected from the group consisting of heteroatomic group, or a linkage thereof, or 3) optionally substituted alkylene or alkenylene optionally interrupted by one or more same or different heteroatomic group; Y is —NR²CO—, —CONR²— wherein R² is hydrogen or lower alkyl, or a group of the formula:

wherein R³ is alkylene; and Ar¹ and Ar² is independently, a carbocycle or heterocycle which is optionally substituted and may have an unsaturated bond; R^(B) is —OH, —NR⁵R⁵′ wherein R⁵ and R⁵′ are independently hydrogen, optionally substituted alkyl, —NH—R, —NH—COR, —NH—CONHR, —O—R wherein each R is independently hydrogen or optionally substituted alkyl or amino sugar residue, or —OR⁶ wherein R⁶ is optionally substituted alkyl that may comprise a heteroatomic group; R^(C) is hydrogen or optionally substituted alkyl that may comprise a heteroatomic group; and R is optionally substituted alkyl.
 8. The compound according to claim 1 represented by the formula:

a pharmaceutically acceptable salt or solvate thereof, wherein, R^(A) is presented by the formula: —X¹—Ar¹—X²—Y—X³—Ar² wherein X¹, X² and X³ are independently 1) single bond; 2) a heteroatom-containing group selected from the group consisting of —N═, ═N—, —NR¹— wherein R¹ is hydrogen or lower alkyl, —O—, —S—, —SO— and —SO₂—, or a linkage thereof; or 3) optionally substituted alkylene or alkenylene optionally interrupted by one or more same or different heteroatomic group; Y is —NR²CO—, —CONR²— wherein R² is hydrogen or lower alkyl, or a group of the formula:

wherein R³ is alkylene; and Ar¹ and Ar² are independently a carbocycle or heterocycle which is optionally substituted and may have an unsaturated bond, R^(B) is —OH, —NR⁵R⁵′ wherein R⁵ and R⁵′ are independently hydrogen, optionally substituted alkyl, —NH—R, —NH—COR, —NH—CONHR, —O—R wherein each R is independently hydrogen or optionally substituted alkyl or amino sugar residue, or —OR⁶ wherein R⁶ is optionally substituted alkyl that may comprise a heteroatomic group; R^(C) is hydrogen or optionally substituted alkyl that may comprise a heteroatomic group, preferably —NH—; and R^(D) is hydrogen or lower alkyl.
 9. The compound according to claim 8 represented by the formula:

or a pharmaceutically acceptable salt or solvate thereof, wherein R^(A) R^(B) R^(C) and R^(D) are as defined in claim
 8. 10. The compound according to claim 7, or a pharmaceutically acceptable salt or solvate thereof, excluding that R^(A) is 4-(monofluorobenzoylamino)benzyl.
 11. The compound according to claim 7, or a pharmaceutically acceptable salt or solvate thereof, excluding that Ar¹ is phenylene; Y is —NR²CO—; and Ar2 is monofluorophenyl.
 12. The compound according to claim 7, or a pharmaceutically acceptable salt or solvate thereof, excluding that Ar² is monofluorophenyl.
 13. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Y is —NR²CO— or —CONR²— and R² is hydrogen or lower alkyl.
 14. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar¹ and Ar² are optionally substituted aryl or optionally substituted heteroaryl or optionally substituted cycloalkyl.
 15. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar¹ and Ar² are optionally substituted aryl, and Y is —NHCO— or —CONH—.
 16. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein X¹ is lower alkylene.
 17. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein X² is a single bond, lower alkylene or the heteroatomic group mentioned above.
 18. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein X³ is a single bond, lower alkylene or the heteroatomic group mentioned above.
 19. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein X¹ is lower alkylene; X² is a single bond, lower alkylene or the heteroatomic group mentioned above; X³ is a single bond, lower alkylene or the heteroatomic group mentioned above; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted phenyl; and Ar² is optionally substituted phenyl, optionally substituted heterocycle or optionally substituted cycloalkyl.
 20. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein X¹ is lower alkylene; X² and X³ are independently a single bond, lower alkylene or the heteroatomic group mentioned above; Y is a group of the formula:

wherein R³ is alkylene; Ar¹ is optionally substituted phenyl; and Ar2 is optionally substituted aryl, optionally substituted heterocycle or optionally substituted cycloalkyl.
 21. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar² is any of aryl, heterocycle or fused rings of the formula:

optionally substituted with one or more substituent selected from the group consisting of lower alkyl, lower alkoxy, cycloalkyl, aryloxy, aralkyloxy, optionally substituted aryloxy lower alkyl, optionally substituted aryloxycarbonyl, lower alkoxycarbonyl, nitro, hydroxy, carboxy, cyano, oxo, SO₂NH₂, SO₂Me, SO₂-cyclic amino, optionally substituted amino, optionally substituted carbamoyl, optionally substituted carbamoyloxy, halo, lower alkyl halide, lower alkoxy halide, lower alkylthio halide, lower alkylcarbonyl halide, heterocyclo lower alkyl, heterocyclo lower alkoxy, cycloalkyl lower alkoxy, aralkyloxy, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl, optionally substituted heteroaryl-lower alkyloxy, heterocycle, heterocycle lower alkyloxy, optionally substituted aryl, and optionally substituted heteroaryl.
 22. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar² is aryl optionally substituted with one or more substituent selected from the group consisting of halo, mono-, di- or tri-halogenated lower alkyl, mono-, di- or tri-halogenated lower alkoxy, mono-, di- or tri-halogenated lower alkylthio, mono- or di-lower alkylamino, cycloalkylmethyloxy, benzyloxy, lower alkoxycarbonylamino, nitro.
 23. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar¹ is phenyl optionally substituted with optionally substituted amino.
 24. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar¹ is optionally substituted heteroaryl.
 25. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein X¹ is lower alkylene; X² is a single bond, lower alkylene or the heteroatomic group mentioned above; X³ is a single bond, lower alkylene or heteroatomic group; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted heteroaryl or optionally substituted heterocycle; and Ar² is optionally substituted phenyl, optionally substituted heterocycle or optionally substituted cycloalkyl.
 26. The compound according to claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein R^(B) is —OH; R^(C) is hydrogen; and R^(D) is hydrogen.
 27. The compound according to claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein R^(B) is —NR⁵R⁵′; R⁵ and R⁵′ are independently hydrogen, optionally substituted alkyl, —NH—R, —NH—COR, —NH—CONHR, —O—R or amino sugar residue; and R is independently hydrogen or optionally substituted alkyl; R^(C) is hydrogen; and R^(D) is hydrogen.
 28. The compound according to claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein R^(B) is —NR⁵R⁵′; R⁵ is hydrogen; R⁵′ is alkyl, —NH—R, —NH—COR, —NH—CONHR, —O—R or amino sugar residue that is substituted with a hydrophilic substituent; R is independently hydrogen or optionally substituted alkyl; R^(C) is hydrogen; and R^(D) is hydrogen.
 29. The compound according to claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein R^(B) is —OH; R^(C) is optionally substituted alkyl that may comprise a heteroatomic group in said alkyl moiety; and R^(D) is hydrogen.
 30. The compound according to claim 8, or a pharmaceutically acceptable salt or solvate thereof, wherein R^(B) is —OH, R^(C) is alkyl that is substituted with a hydrophilic substituent and may comprise a heteroatomic group in said alkyl moiety; and R^(D) is hydrogen.
 31. The compound according to claim 7, or a pharmaceutically acceptable salt or solvate thereof, wherein X¹ is lower alkylene; X² is a single bond, lower alkylene or heteroatomic group; X³ is a single bond, lower alkylene or heteroatomic group; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted phenyl, optionally substituted heteroaryl or optionally substituted heterocycle; Ar² is optionally substituted phenyl, optionally substituted heterocycle or optionally substituted cycloalkyl; and wherein the compound meets at least one of the requirements 1)-3) for R^(B), R^(C) and R^(D): 1) R^(B) is —NR⁵R⁵′ wherein R⁵ and R⁵′ are independently hydrogen, optionally substituted alkyl, —NH—R, —NH—COR, —NH—CONHR, —O—R or amino sugar residue; and R is independently hydrogen or optionally substituted alkyl; 2)R^(C) is optionally substituted alkyl in which alkyl moiety may be interrupted with a heteroatomic group; 3)R^(D) is lower alkyl.
 32. The compound according to claim 1 represented by of the formula:

or a pharmaceutically acceptable salt or solvate thereof, wherein, R^(A) is the formula —X¹—Ar¹—X²—Y—X³—Ar² wherein, X¹, X² and X³ are independently 1) single bond; 2) a heteroatom or heteroatomic group, selected from the group consisting of —N═, ═N—, —NR¹—, —O—, —S—, —SO— and —SO₂— wherein R¹ is hydrogen or lower alkyl; or 3) optionally substituted alkylene or alkenylene optionally interrupted by one or more same or different heteroatomic group; Y is —NR²CO—, —CONR²— wherein R² is hydrogen or lower alkyl, or a group represented by the formula:

wherein, R³ is alkylene; and Ar¹ and Ar² are independently a carbocycle or heterocycle which is optionally substituted and may have an unsaturated bond, R^(B) is —OH or —NR⁵R⁵′ wherein R⁵ and R⁵′ are independently hydrogen or optionally substituted alkyl; R^(C) is hydrogen or optionally substituted alkyl that may comprise a heteroatomic group; and R^(D) is hydrogen or lower alkyl.
 33. The compound according to claim 32, or a pharmaceutically acceptable salt or solvate thereof, wherein X¹ is lower alkylene; X² is a single bond or lower alkylene that may comprise a heteroatomic group; X³ is a single bond; Y is —NHCO— or —CONH—; Ar¹ is optionally substituted phenyl; Ar² is optionally substituted phenyl; R^(B) is OH; and R^(C) and R^(D) are hydrogen. 